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Here we show epidermal 1\u2010OACs arise shortly before birth during the establishment of the water permeability barrier in mice. Fractionation of human epidermis indicates 1\u2010OACs concentrate in the stratum corneum. During in vitro maturation into reconstructed human epidermis, human keratinocytes dramatically increase 1\u2010OAC levels indicating they are one source of epidermal 1\u2010OACs. In search of potential enzymes responsible for 1\u2010OAC synthesis in vivo, we analyzed mutant mice with deficiencies of ceramide synthases (Cers2, Cers3, or Cers4), diacylglycerol acyltransferases (Dgat1 or Dgat2), elongase of very long fatty acids 3 (Elovl3), lecithin cholesterol acyltransferase (Lcat), stearoyl\u2010CoA desaturase 1 (Scd1), or acidic ceramidase (Asah1). Overall levels of 1\u2010OACs did not decrease in any mouse model. In Cers3 and Dgat2\u2010deficient epidermis they even increased in correlation with deficient skin barrier function. Dagt2 deficiency reshapes 1\u2010OAC synthesis with an increase in 1\u2010OACs with N\u2010linked non\u2010hydroxylated fatty acids and a 60% decrease compared to control in levels of 1\u2010OACs with N\u2010linked hydroxylated palmitate. As none of the single enzyme deficiencies we examined resulted in a lack of 1\u2010OACs, we conclude that either there is functional redundancy in forming 1\u2010OAC and more than one enzyme is involved, and\/or an unknown acyltransferase of the epidermis performs the final step of 1\u2010OAC synthesis, the implications of which are discussed.<\/jats:p>","DOI":"10.1002\/lipd.12342","type":"journal-article","created":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T03:51:38Z","timestamp":1648007498000},"page":"183-195","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Epidermal <scp>1\u2010<\/scp><i>O<\/i>\u2010acylceramides appear with the establishment of the water permeability barrier in mice and are produced by maturating keratinocytes"],"prefix":"10.1002","volume":"57","author":[{"given":"Mariona","family":"Rabionet","sequence":"first","affiliation":[{"name":"Lipid Pathobiochemistry Group German Cancer Research Center  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pauline","family":"Bernard","sequence":"additional","affiliation":[{"name":"Infinity, Universit\u00e9 Toulouse, CNRS, Inserm, UPS  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Pichery","sequence":"additional","affiliation":[{"name":"Infinity, Universit\u00e9 Toulouse, CNRS, Inserm, UPS  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Marsching","sequence":"additional","affiliation":[{"name":"Lipid Pathobiochemistry Group German Cancer Research Center  Heidelberg Germany"},{"name":"Center for Applied Research in Biomedical Mass Spectrometry (ABIMAS)  Mannheim Germany"},{"name":"Center for Mass Spectrometry and Optical Spectroscopy (CeMOS) Mannheim University of Applied Sciences  Mannheim Germany"},{"name":"Instrumental Analytics and Bioanalytics Mannheim University of Applied Sciences  Mannheim Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline","family":"Bayerle","sequence":"additional","affiliation":[{"name":"Lipid Pathobiochemistry Group German Cancer Research Center  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaalee","family":"Dworski","sequence":"additional","affiliation":[{"name":"Institute of Medical Sciences University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa A.","family":"Kamani","sequence":"additional","affiliation":[{"name":"University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandramohan","family":"Chitraju","sequence":"additional","affiliation":[{"name":"Department of Genetics and Complex Diseases Harvard T.H. 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