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Emerging evidence links dysregulation of LA and its metabolites to various skin disorders, including acne vulgaris, atopic dermatitis, and psoriasis vulgaris. While reviews exist on the physiological roles of LA in human health, a dedicated synthesis focusing on its enzymatic metabolism within the skin remains absent. Capitalising on the skin's distinctive structural and enzymatic features, this review aims to synthesise current knowledge on linoleic acid metabolism while illuminating novel insights that reveal the previously underappreciated complexity of cutaneous LA\u2010mediated lipid signalling networks. (i) Linoleic acid undergoes three primary metabolic transformations in skin tissue: (a) serving as a substrate for \u03b2\u2010oxidation, (b) participating in lipid biosynthesis and conversion, and (c) undergoing enzymatic non\u2010catabolic oxidation to form bioactive lipid mediators. (ii) In the epidermis, LA primarily influences keratinocyte function through lipid biosynthesis and enzymatic oxidation pathways. In the dermis, LA predominantly affects sebaceous gland cells via \u03b2\u2010oxidation and lipid biosynthesis\/conversion pathways. (iii) Further studies could concentrate on (a) the crosstalk between competing non\u2010catabolic oxidative routes (Lipoxygenases\/Cytochrome P450 enzymes\/Cyclooxygenases); (b) the paradoxical regulatory mechanisms controlling Lipoxygenases activation\/inactivation; (c) the possible existence of linoleic acid\/arachidonic acid (AA) intermediate in non\u2010sebaceous cells; (d) the divergent biological roles of LA versus AA in sebocyte regulation; and (e) the emerging evidence of oxidative stress as a positive modulator of sebum production.<\/jats:p>","DOI":"10.1111\/exd.70229","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T04:30:21Z","timestamp":1771821021000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Skin Metabolism of Linoleic Acid: Enzymatic Pathways and Roles in Skin Homeostasis"],"prefix":"10.1111","volume":"35","author":[{"given":"Mengyuan","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Plastic &amp; Reconstructive Surgery Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiyuan","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Plastic &amp; Reconstructive Surgery Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Plastic &amp; Reconstructive Surgery Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,2,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MCO.0000000000001096"},{"issue":"8","key":"e_1_2_11_3_1","first-page":"248","article-title":"A New Deficiency Disease Produced by the Rigid Exclusion of Fat From the Diet","volume":"31","author":"Burr G. 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