{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n LCE1D is a member of the late cornified envelope (LCE) gene family within the epidermal differentiation complex (EDC) that encodes structural proteins essential for forming the cornified cell envelope—a key element in establishing skin barrier function. A stop codon mutation in LCE1D has been identified in individuals with eczema, suggesting that disruption of this gene’s normal function may impair the integrity and proper assembly of the cornified envelope, thus contributing to skin barrier dysfunction and related inflammatory skin conditions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In addition, studies of EDC gene regulation have revealed that LCE family members are modulators of keratinocyte differentiation; for instance, overexpression of the transcription factor GRHL2 represses several EDC genes—including LCEs—thereby impairing normal keratinocyte maturation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " Moreover, LCE1 genes have been shown to be novel downstream targets of p53; activation of p53 following DNA damage directly enhances the expression of these genes, which in turn may contribute to tumor suppressor activities by modulating the function of other regulatory proteins such as PRMT5."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": " Collectively, these observations suggest that LCE1D plays an important role in epidermal differentiation and barrier function, and that its disruption—whether through genetic mutations or altered regulation—could contribute to skin pathologies such as eczema and possibly influence responses to cellular stress.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ingo Marenholz, Vladimir A Gimenez Rivera, Jorge Esparza-Gordillo, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Association screening in the Epidermal Differentiation Complex (EDC) identifies an SPRR3 repeat number variant as a risk factor for eczema."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Invest Dermatol (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/jid.2011.90"}], "href": "https://doi.org/10.1038/jid.2011.90"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21490620"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21490620"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "W Chen, Z Xiao Liu, J-E Oh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Grainyhead-like 2 (GRHL2) inhibits keratinocyte differentiation through epigenetic mechanism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cddis.2012.190"}], "href": "https://doi.org/10.1038/cddis.2012.190"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23254293"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23254293"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Zhenzhong Deng, Koichi Matsuda, Chizu Tanikawa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Late Cornified Envelope Group I, a novel target of p53, regulates PRMT5 activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neoplasia (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.neo.2014.07.008"}], "href": "https://doi.org/10.1016/j.neo.2014.07.008"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "25220593"}], "href": "https://pubmed.ncbi.nlm.nih.gov/25220593"}]}]}]}