{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:39:27Z","timestamp":1792687167585,"version":"4.5.0"},"reference-count":0,"publisher":"American Society for Clinical Investigation","license":[{"start":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T00:00:00Z","timestamp":1792627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["K08-AR075846"],"award-info":[{"award-number":["K08-AR075846"]}]},{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["R03-AR082896"],"award-info":[{"award-number":["R03-AR082896"]}]},{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["P30-AR075043"],"award-info":[{"award-number":["P30-AR075043"]}]},{"name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","award":["P30-AR069589"],"award-info":[{"award-number":["P30-AR069589"]}]},{"name":"LEO Foundation","award":["LF-OC-23-001393"],"award-info":[{"award-number":["LF-OC-23-001393"]}]},{"name":"Foundation for Ichthyosis and Related Skin Types","award":["Research Grant"],"award-info":[{"award-number":["Research Grant"]}]},{"name":"Taubman Medical Research Institute","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"name":"American Skin Association","award":["Bristol Myers Squibb Research Grant"],"award-info":[{"award-number":["Bristol Myers Squibb Research Grant"]}]},{"name":"National Center for Advancing Translational Sciences","award":["R03-TR005428"],"award-info":[{"award-number":["R03-TR005428"]}]},{"name":"American Society for Clinical Investigation","award":["Physician-Scientist Support Foundation Fellowship"],"award-info":[{"award-number":["Physician-Scientist Support Foundation Fellowship"]}]},{"name":"National Psoriasis Foundation","award":["852098"],"award-info":[{"award-number":["852098"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:p>Differentiating keratinocytes break down their organelles and nuclei to become the compacted cornified layers of the epidermal barrier in a poorly understood catabolic process. Live confocal imaging of stratified human organotypic epidermis revealed endoplasmic reticulum (ER) fragmentation and lysosomal engulfment in the cornifying layers, where we found up-regulation of TEX264, a receptor that mediates selective autophagy of the ER (reticulophagy). TEX264 expression was increased by ER stress, which caused precocious cornification of organotypic epidermis. In undifferentiated keratinocytes, ectopic TEX264 was sufficient to induce ER fragments, while in highly differentiated keratinocytes, it accelerated ER elimination and nuclear shrinkage; these effects were abolished by mutating the LC3 interacting region required for its autophagic function. Knockout of TEX264 or inhibiting its activation disrupted the maturation of organotypic cultures, pointing to a critical role for reticulophagy in cornification. Finally, in patient biopsies and an organotypic model of Darier disease, a genetic cornification disorder linked to ER dysfunction, we found increased TEX264 in areas of premature cornification (dyskeratosis). Our results identified TEX264 as a key driver of late-stage epidermal differentiation and led us to propose a model of cornification in which keratinocytes activate selective autophagy receptors to orchestrate orderly organelle elimination during cutaneous barrier formation.<\/jats:p>","DOI":"10.1172\/jci.insight.196831","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:00:51Z","timestamp":1792684851000},"source":"Crossref","is-referenced-by-count":0,"title":["The endoplasmic reticulum autophagy receptor TEX264 drives epidermal differentiation and is dysregulated in Darier disease"],"prefix":"10.1172","author":[{"given":"Christopher J.","family":"Johnson","sequence":"first","affiliation":[{"name":"Department of Dermatology, University of Washington, Seattle, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4327-7934","authenticated-orcid":true,"given":"Afua","family":"Tiwaa","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Washington, Seattle, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arti","family":"Parihar","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Washington, Seattle, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edwin","family":"Antonio","sequence":"additional","affiliation":[{"name":"University of Washington School of Medicine, Seattle, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brooke D.","family":"Lorenz","sequence":"additional","affiliation":[{"name":"University of Washington School of Medicine, Seattle, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reeteka","family":"Kudallur","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Washington, Seattle, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aaron","family":"Ramonett","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine & Pathology, University of Washington, Seattle, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Coon","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8505-4259","authenticated-orcid":true,"given":"Mrinal K.","family":"Sarkar","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0080-0812","authenticated-orcid":true,"given":"Johann","family":"Gudjonsson","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Michigan, Ann Arbor, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3933-6404","authenticated-orcid":true,"given":"Cory L.","family":"Simpson","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University of Washington, Seattle, United States of America"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,10,22]]},"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/insight.jci.org\/articles\/view\/196831\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:00:54Z","timestamp":1792684854000},"score":1,"resource":{"primary":{"URL":"http:\/\/insight.jci.org\/articles\/view\/196831"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,22]]},"references-count":0,"alternative-id":["10.1172\/jci.insight.196831"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.196831","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,22]]}}}