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

    <schemaVersion>X0609</schemaVersion>

    <documentType>4</documentType>

    <periodOfReport>2026-08-26</periodOfReport>

    <issuer>
        <issuerCik>0001699350</issuerCik>
        <issuerName>SHOULDER INNOVATIONS, INC.</issuerName>
        <issuerTradingSymbol>SI</issuerTradingSymbol>
        <issuerForeignTradingSymbol></issuerForeignTradingSymbol>
    </issuer>

    <reportingOwner>
        <reportingOwnerId>
            <rptOwnerCik>0001420106</rptOwnerCik>
            <rptOwnerName>Gilde Healthcare Holding B.V.</rptOwnerName>
        </reportingOwnerId>
        <reportingOwnerAddress>
            <rptOwnerNonUSAddressFlag>true</rptOwnerNonUSAddressFlag>
            <rptOwnerStreet1>STADSPLATEAU 36</rptOwnerStreet1>
            <rptOwnerStreet2></rptOwnerStreet2>
            <rptOwnerCity>UTRECHT</rptOwnerCity>
            <rptOwnerNonUSStateTerritory>NETHERLANDS</rptOwnerNonUSStateTerritory>
            <rptOwnerCountry>P7</rptOwnerCountry>
            <rptOwnerZipCode>3521 AZ</rptOwnerZipCode>
            <rptOwnerStateDescription>NETHERLANDS</rptOwnerStateDescription>
        </reportingOwnerAddress>
        <reportingOwnerRelationship>
            <isDirector>false</isDirector>
            <isOfficer>false</isOfficer>
            <isTenPercentOwner>true</isTenPercentOwner>
            <isOther>false</isOther>
        </reportingOwnerRelationship>
    </reportingOwner>

    <aff10b5One>false</aff10b5One>

    <nonDerivativeTable>
        <nonDerivativeTransaction>
            <securityTitle>
                <value>Common Stock</value>
            </securityTitle>
            <transactionDate>
                <value>2026-08-26</value>
            </transactionDate>
            <transactionCoding>
                <transactionFormType>4</transactionFormType>
                <transactionCode>S</transactionCode>
                <equitySwapInvolved>false</equitySwapInvolved>
            </transactionCoding>
            <transactionAmounts>
                <transactionShares>
                    <value>1196</value>
                </transactionShares>
                <transactionPricePerShare>
                    <value>22.60</value>
                </transactionPricePerShare>
                <transactionAcquiredDisposedCode>
                    <value>D</value>
                </transactionAcquiredDisposedCode>
            </transactionAmounts>
            <postTransactionAmounts>
                <sharesOwnedFollowingTransaction>
                    <value>2185914</value>
                </sharesOwnedFollowingTransaction>
            </postTransactionAmounts>
            <ownershipNature>
                <directOrIndirectOwnership>
                    <value>I</value>
                    <footnoteId id="F1"/>
                </directOrIndirectOwnership>
                <natureOfOwnership>
                    <value>See footnote</value>
                    <footnoteId id="F1"/>
                </natureOfOwnership>
            </ownershipNature>
        </nonDerivativeTransaction>
    </nonDerivativeTable>

    <footnotes>
        <footnote id="F1">Held directly by Cooperatieve Gilde Healthcare V U.A. (&quot;Gilde&quot;). Gilde Healthcare V Management B.V. is the managing director of Gilde and has sole voting and dispositive power with respect to the shares held by Gilde. Gilde Healthcare V Management B.V. is owned by Gilde Healthcare Holding B.V. The managing partners of Gilde Healthcare Holding B.V. are Manapouri B.V. (of which Edwin de Graaf is the owner and managing director) and Martemanshurk B.V. (of which Pieter van der Meer is the owner and managing director). Geoff Pardo is a partner at Gilde and may be deemed to share voting and dispositive power with respect to the shares held of record by Gilde. Mr. Pardo disclaims beneficial ownership of such holdings, except to the extent of his pecuniary interest in the shares.</footnote>
    </footnotes>

    <ownerSignature>
        <signatureName>Gilde Healthcare Holding B.V., By: /s/ Edwin de Graaf, Managing Director</signatureName>
        <signatureDate>2026-08-28</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>Gilde Healthcare V Management B.V., By: /s/ Edwin de Graaf, Managing Director</signatureName>
        <signatureDate>2026-08-28</signatureDate>
    </ownerSignature>

    <ownerSignature>
        <signatureName>Cooperatieve Gilde Healthcare V U.A., By: /s/ Edwin de Graaf, Managing Director</signatureName>
        <signatureDate>2026-08-28</signatureDate>
    </ownerSignature>
</ownershipDocument>
