<?xml version="1.0"?>
<ownershipDocument>

    <schemaVersion>X0306</schemaVersion>

    <documentType>4</documentType>

    <periodOfReport>2016-11-21</periodOfReport>

    <notSubjectToSection16>0</notSubjectToSection16>

    <issuer>
        <issuerCik>0001445283</issuerCik>
        <issuerName>PROTEOSTASIS THERAPEUTICS, INC.</issuerName>
        <issuerTradingSymbol>PTI</issuerTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001583977</rptOwnerCik>
            <rptOwnerName>Cormorant Asset Management, LLC</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>200 CLARENDON STREET, 52ND FLOOR</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>BOSTON</rptOwnerCity>
            <rptOwnerState>MA</rptOwnerState>
            <rptOwnerZipCode>02116</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>0</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>1</isTenPercentOwner>
            <isOther>0</isOther>
            <officerTitle></officerTitle>
            <otherText></otherText>
        </reportingOwnerRelationship>
    </reportingOwner>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001599214</rptOwnerCik>
            <rptOwnerName>Chen Bihua</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>C/O CORMORANT ASSET MANAGEMENT, LLC</rptOwnerStreet1>
            <rptOwnerStreet2>200 CLARENDON STREET, 52ND FLOOR</rptOwnerStreet2>
            <rptOwnerCity>BOSTON</rptOwnerCity>
            <rptOwnerState>MA</rptOwnerState>
            <rptOwnerZipCode>02116</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>1</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>1</isTenPercentOwner>
            <isOther>0</isOther>
            <officerTitle></officerTitle>
            <otherText></otherText>
        </reportingOwnerRelationship>
    </reportingOwner>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001618451</rptOwnerCik>
            <rptOwnerName>Cormorant Global Healthcare GP, LLC</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>200 CLARENDON STREET, 52ND FLOOR</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>BOSTON</rptOwnerCity>
            <rptOwnerState>MA</rptOwnerState>
            <rptOwnerZipCode>02116</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>0</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>1</isTenPercentOwner>
            <isOther>0</isOther>
            <officerTitle></officerTitle>
            <otherText></otherText>
        </reportingOwnerRelationship>
    </reportingOwner>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001618442</rptOwnerCik>
            <rptOwnerName>Cormorant Global Healthcare Master Fund, LP</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerStreet1>200 CLARENDON STREET, 52ND FLOOR</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>BOSTON</rptOwnerCity>
            <rptOwnerState>MA</rptOwnerState>
            <rptOwnerZipCode>02116</rptOwnerZipCode>
            <rptOwnerStateDescription></rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>0</isDirector>
            <isOfficer>0</isOfficer>
            <isTenPercentOwner>1</isTenPercentOwner>
            <isOther>0</isOther>
            <officerTitle></officerTitle>
            <otherText></otherText>
        </reportingOwnerRelationship>
    </reportingOwner>

    <nonDerivativeTable>
        <nonDerivativeTransaction>
            <securityTitle>
                <value>Common Stock</value>
            </securityTitle>
            <transactionDate>
                <value>2016-11-21</value>
            </transactionDate>
            <deemedExecutionDate></deemedExecutionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>P</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>111863</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>11.6448</value>
                    <footnoteId id="F3"/>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>3129945</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See Footnotes</value>
                    <footnoteId id="F1"/>
                    <footnoteId id="F2"/>
                    <footnoteId id="F3"/>
                </natureOfOwnership>
            </ownershipNature>
        </nonDerivativeTransaction>
        <nonDerivativeTransaction>
            <securityTitle>
                <value>Common Stock</value>
            </securityTitle>
            <transactionDate>
                <value>2016-11-22</value>
            </transactionDate>
            <deemedExecutionDate></deemedExecutionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>P</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>69500</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>11.0765</value>
                    <footnoteId id="F4"/>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>3199445</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See Footnotes</value>
                    <footnoteId id="F1"/>
                    <footnoteId id="F2"/>
                    <footnoteId id="F4"/>
                </natureOfOwnership>
            </ownershipNature>
        </nonDerivativeTransaction>
        <nonDerivativeTransaction>
            <securityTitle>
                <value>Common Stock</value>
            </securityTitle>
            <transactionDate>
                <value>2016-11-23</value>
            </transactionDate>
            <deemedExecutionDate></deemedExecutionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>P</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>180300</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>11.372</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>3379745</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See Footnotes</value>
                    <footnoteId id="F1"/>
                    <footnoteId id="F2"/>
                    <footnoteId id="F5"/>
                </natureOfOwnership>
            </ownershipNature>
        </nonDerivativeTransaction>
        <nonDerivativeTransaction>
            <securityTitle>
                <value>Common Stock</value>
            </securityTitle>
            <transactionDate>
                <value>2016-11-23</value>
            </transactionDate>
            <deemedExecutionDate></deemedExecutionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>P</transactionCode>
                <equitySwapInvolved>0</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>200</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>10.67</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>A</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>3379945</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See Footnotes</value>
                    <footnoteId id="F1"/>
                    <footnoteId id="F2"/>
                    <footnoteId id="F6"/>
                </natureOfOwnership>
            </ownershipNature>
        </nonDerivativeTransaction>
    </nonDerivativeTable>

    <derivativeTable></derivativeTable>

    <footnotes>
        <footnote id="F1">Shares reported herein are held by Cormorant Global Healthcare Master Fund, LP (the &quot;Master Fund&quot;) and by a managed account (the &quot;Account&quot;). Cormorant Asset Management, LLC (&quot;Cormorant&quot;) serves as the investment manager of the Master Fund and the Account. Cormorant Global Healthcare GP, LLC (&quot;GP LLC&quot;) serves as General Partner of the Master Fund. Bihua Chen serves as manager of Cormorant and GP LLC. GP LLC may be deemed to beneficially own the shares held by the Master Fund, and Cormorant and Ms. Chen may be deemed to beneficially own the shares held by the Master Fund and the Account.</footnote>
        <footnote id="F2">Each of the Reporting Persons disclaims beneficial ownership of the shares reported herein except to the extent of its or her pecuniary interest therein, and the filing of this Form 4 shall not be construed as an admission that any of the Reporting Persons is the beneficial owner of any such shares for purposes of Section 16(a) of the Securities Exchange Act of 1934 or for any other purpose.</footnote>
        <footnote id="F3">Represents the weighted average purchase price of shares purchased in a series of open market transactions on the transaction date at prices ranging from $11.325 to $11.75 per share. The Reporting Persons undertake to provide, upon request by the staff of the Securities and Exchange Commission, the issuer, or a security holder of the issuer, full information regarding the number of shares purchased at each price. Of these shares, 93,014 were purchased for the Master Fund and 18,849 shares were purchased for the Account. As of November 21, 2016, the Master Fund held 2,609,501 shares, and the Account held 520,444 shares.</footnote>
        <footnote id="F4">Represents the weighted average purchase price of shares purchased in a series of open market transactions on the transaction date at prices ranging from $10.72 to $11.25 per share. The Reporting Persons undertake to provide, upon request by the staff of the Securities and Exchange Commission, the issuer, or a security holder of the issuer, full information regarding the number of shares purchased at each price. Of these shares, 57,790 were purchased for the Master Fund and 11,710 shares were purchased for the Account. As of November 22, 2016, the Master Fund held 2,667,291 shares, and the Account held 532,154 shares.</footnote>
        <footnote id="F5">Represents the weighted average purchase price of shares purchased in a series of open market transactions on the transaction date at prices ranging from $10.96 to $11.75 per share. The Reporting Persons undertake to provide, upon request by the staff of the Securities and Exchange Commission, the issuer, or a security holder of the issuer, full information regarding the number of shares purchased at each price. Of these shares, 149,919 were purchased for the Master Fund and 30,381 shares were purchased for the Account.</footnote>
        <footnote id="F6">Of these shares, 166 were purchased for the Master Fund and 34 shares were purchased for the Account.  As of November 23, 2016, the Master Fund held 2,817,376 shares, and the Account held 562,569 shares.</footnote>
    </footnotes>

    <ownerSignature>
        <signatureName>/s/ CORMORANT GLOBAL HEALTHCARE GP, LLC By: Bihua Chen, Managing Member</signatureName>
        <signatureDate>2016-11-23</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>/s/ CORMORANT ASSET MANAGEMENT, LLC By: Bihua Chen, Managing Member</signatureName>
        <signatureDate>2016-11-23</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>/s/ CORMORANT GLOBAL HEALTHCARE MASTER FUND, LP By: Cormorant Global Healthcare GP, LLC, its General Partner By: Bihua Chen, Managing Member</signatureName>
        <signatureDate>2016-11-23</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>/s/ Bihua Chen</signatureName>
        <signatureDate>2016-11-23</signatureDate>
    </ownerSignature>
</ownershipDocument>
