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Here, we demonstrate that Mfsd2a, a lysophosphatidylcholine (LPC) transporter, is predominantly expressed in keratinocytes and mediates the uptake of a plasma-derived LPC fluorescent probe. Epidermal-specific deficiency of Mfsd2a in mice resulted in dermatitis and defective desquamation of the epidermis, and inducible deletion of\n                    <jats:italic toggle=\"yes\">Mfsd2a<\/jats:italic>\n                    in primary mouse keratinocytes in vitro prevented their epidermal stratification. Untargeted lipidomic analysis indicated that Mfsd2a deficiency resulted in a significantly altered phospholipidome, with specific reductions in linoleic acid in phosphatidylcholine and triglycerides in the epidermis. Functional studies using primary human keratinocytes demonstrated that LPC-oleate and LPC-linoleate promoted keratinocyte differentiation in a Mfsd2a-dependent manner. Our findings identify a pathway by which keratinocytes acquire plasma-derived LPC via Mfsd2a transport for the maintenance of normal keratinocyte phosphatidylcholine pools and for optimal keratinocyte differentiation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2531159123","type":"journal-article","created":{"date-parts":[[2026,2,19]],"date-time":"2026-02-19T18:35:56Z","timestamp":1771526156000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":2,"title":["Mfsd2a is important for maintaining epidermal homeostasis"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8981-1376","authenticated-orcid":false,"given":"Bernice H.","family":"Wong","sequence":"first","affiliation":[{"name":"Signature Research Program in Cardiovascular and Metabolic Disorders, Duke\u2013National University of Singapore Medical School","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0460-2554","authenticated-orcid":false,"given":"Kunal","family":"Mishra","sequence":"additional","affiliation":[{"name":"Signature Research Program in Cardiovascular and Metabolic Disorders, Duke\u2013National University of Singapore Medical School","place":["Singapore, Singapore"]},{"name":"Centre for Computational Biology, Duke\u2013National University of Singapore Medical School","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6753-9228","authenticated-orcid":false,"given":"Cheen Fei","family":"Chin","sequence":"additional","affiliation":[{"name":"Signature Research Program in Cardiovascular and Metabolic Disorders, Duke\u2013National University of Singapore Medical School","place":["Singapore, Singapore"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dwight L. 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