{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T19:45:12Z","timestamp":1790624712501,"version":"4.1.0"},"reference-count":129,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T00:00:00Z","timestamp":1643241600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Keratohyalin granules were discovered in the mid-19th century in cells that terminally differentiate to form the outer, cornified layer of the epidermis. The first indications of the composition of these structures emerged in the 1960s from a histochemical stain for histidine, followed by radioautographic evidence of a high incidence of histidine incorporation into newly synthesized proteins in cells containing the granules. Research during the next three decades revealed the structure and function of a major protein in these granules, which was initially called the \u2018histidine-rich protein\u2019. Steinert and Dale named the protein \u2018filaggrin\u2019 in 1981 because of its ability to aggregate keratin intermediate filaments. The human gene for the precursor, \u2018profilaggrin,\u2019 was reported in 1991 to encode 10, 11 or 12 nearly identical repeats. Remarkably, the mouse and rat genes encode up to 20 repeats. The lifetime of filaggrin is the time required for keratinocytes in the granular layer to move into the inner cornified layer. During this transition, filaggrin facilitates the collapse of corneocytes into \u2018building blocks\u2019 that become an impermeable surface barrier. The subsequent degradation of filaggrin is as remarkable as its synthesis, and the end-products aid in maintaining moisture in the cornified layer. It was apparent that ichthyosis vulgaris and atopic dermatitis were associated with the absence of this protein. McLean\u2019s team in 2006 identified the cause of these diseases by discovering loss-of-function mutations in the profilaggrin gene, which led to dysfunction of the surface barrier. This story illustrates the complexity in maintaining a healthy, functional epidermis.<\/jats:p>","DOI":"10.3390\/ijms23031455","type":"journal-article","created":{"date-parts":[[2022,1,27]],"date-time":"2022-01-27T22:00:56Z","timestamp":1643320856000},"page":"1455","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["The Discovery and Function of Filaggrin"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0250-9970","authenticated-orcid":false,"given":"J. Kenneth","family":"Hoober","sequence":"first","affiliation":[{"name":"Susavion Biosciences, Inc., 1615 W University Drive, Suite 132, Tempe, AZ 85281, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura L.","family":"Eggink","sequence":"additional","affiliation":[{"name":"Susavion Biosciences, Inc., 1615 W University Drive, Suite 132, Tempe, AZ 85281, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"s84","DOI":"10.1038\/jid.1989.36","article-title":"Biologic structure and function: Perspectives on morphologic approaches to the study of the granular layer keratinocyte","volume":"92","author":"Holbrook","year":"1989","journal-title":"J. Investig. Dermatol."},{"key":"ref_2","unstructured":"Montagna, W., and Lobitz, W.C. (1964). Keratinization in historical perspective. 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