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In this study, we investigated the non\u2010proteinogenic amino acid L\u20104\u2010Thiazolylalanine (L4) as a potential active ingredient in skin protection and barrier strength.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>L4 on wound healing, anti\u2010inflammatory and anti\u2010oxidant properties were evaluated using monolayers and 3D skin equivalents. The transepithelial electrical resistance (TEER) value was used in vitro as a strong indicator of barrier strength and integrity. Clinical L4 efficacy was assessed for the evaluation of the skin barrier integrity and soothing benefits.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In vitro treatments of L4 show beneficial effects in wound closure mechanism, and we demonstrate that L4 anti\u2010oxidant benefits with markedly increased HSP70 and decreased reactive oxygen species production induced by UVs exposure. Barrier strength and integrity were significantly improved by L4, confirmed clinically by an increase in 12R\u2010lipoxygenase enzymatic activity in the stratum corneum. In addition, soothing benefits of L4 have been shown clinically with the decrease in redness after methyl nicotinate application on the inner arm and the significant reduction of the erythema and the skin desquamation on the scalp.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>L4 delivered multiple skin benefits by strengthening the skin barrier, accelerating the skin repair process as well as soothing the skin and the scalp with anti\u2010inflammaging effects. The observed efficacy validates L4 as a desirable skincare ingredient for topical treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ics.12881","type":"journal-article","created":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T15:35:19Z","timestamp":1688484919000},"page":"725-738","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Effect of <scp>L\u20104\u2010Thiazolylalanine<\/scp> (Protinol\u2122) on skin barrier strength and skin protection"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5463-3546","authenticated-orcid":false,"given":"C.","family":"Haxaire","sequence":"first","affiliation":[{"name":"Avon Skin Care Institute, Global Research and Development Avon Products Inc.  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