{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:37:14Z","timestamp":1792669034186,"version":"4.5.0"},"reference-count":285,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T00:00:00Z","timestamp":1652140800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Austrian Science Fund","award":["FWF 31662"],"award-info":[{"award-number":["FWF 31662"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The discovery in 2006 that loss-of-function mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and can predispose to atopic dermatitis (AD) galvanized the dermatology research community and shed new light on a skin protein that was first identified in 1981. However, although outstanding work has uncovered several key functions of filaggrin in epidermal homeostasis, a comprehensive understanding of how filaggrin deficiency contributes to AD is still incomplete, including details of the upstream factors that lead to the reduced amounts of filaggrin, regardless of genotype. In this review, we re-evaluate data focusing on the roles of filaggrin in the epidermis, as well as in AD. Filaggrin is important for alignment of keratin intermediate filaments, control of keratinocyte shape, and maintenance of epidermal texture via production of water-retaining molecules. Moreover, filaggrin deficiency leads to cellular abnormalities in keratinocytes and induces subtle epidermal barrier impairment that is sufficient enough to facilitate the ingress of certain exogenous molecules into the epidermis. However, although FLG null mutations regulate skin moisture in non-lesional AD skin, filaggrin deficiency per se does not lead to the neutralization of skin surface pH or to excessive transepidermal water loss in atopic skin. Separating facts from chaff regarding the functions of filaggrin in the epidermis is necessary for the design efficacious therapies to treat dry and atopic skin.<\/jats:p>","DOI":"10.3390\/ijms23105318","type":"journal-article","created":{"date-parts":[[2022,5,10]],"date-time":"2022-05-10T08:31:55Z","timestamp":1652171515000},"page":"5318","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":167,"title":["Revisiting the Roles of Filaggrin in Atopic Dermatitis"],"prefix":"10.3390","volume":"23","author":[{"given":"Verena","family":"Moosbrugger-Martinz","sequence":"first","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Anichstra\u00dfe 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Leprince","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Toulouse University, CNRS UMR5051, Inserm UMR1291, UPS, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8915-8223","authenticated-orcid":false,"given":"Marie-Claire","family":"M\u00e9chin","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Toulouse University, CNRS UMR5051, Inserm UMR1291, UPS, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3655-6329","authenticated-orcid":false,"given":"Michel","family":"Simon","sequence":"additional","affiliation":[{"name":"Toulouse Institute for Infectious and Inflammatory Diseases (Infinity), Toulouse University, CNRS UMR5051, Inserm UMR1291, UPS, 31059 Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Blunder","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Anichstra\u00dfe 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Gruber","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Anichstra\u00dfe 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2936-8488","authenticated-orcid":false,"given":"Sandrine","family":"Dubrac","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Venereology and Allergology, Medical University of Innsbruck, Anichstra\u00dfe 35, 6020 Innsbruck, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1159\/000396298","article-title":"Stratum corneum basic protein: An interfilamentous matrix protein of epidermal keratin","volume":"10","author":"Dale","year":"1980","journal-title":"Curr. 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