LCE3E (late cornified envelope 3E) is a structural protein precursor that contributes to cornified envelope formation in the stratum corneum, the outermost layer of skin 1. As a member of the late cornified envelope gene family, LCE3E participates in keratinocyte differentiation and keratinization processes essential for skin barrier integrity 23. The gene exhibits protein-binding capacity and functions in cross-linking processes during epidermal development 3. LCE3E has significant disease relevance across multiple skin conditions. Genetic variants in the LCE3D-LCE3E locus are associated with psoriasis susceptibility, with particular importance in patients carrying deletions of LCE3B and LCE3C who may rely on compensatory expression of LCE3E 41. In atopic dermatitis, LCE3E functions as a hub gene orchestrating keratinization pathways and represents a potential therapeutic target 5. Notably, LCE3E expression is downregulated in diabetic foot ulcers, suggesting impaired wound healing capacity 3. Additionally, LCE3E expression correlates with angiolymphatic invasion and poor survival outcomes in laryngeal squamous cell carcinoma 6. Clinically, dietary vitamin D receptor ligands such as docosahexaenoic acid and curcumin can induce LCE3E expression and suppress TNFα-mediated inflammatory signaling, offering therapeutic potential for mild-to-moderate psoriasis 1. Understanding LCE3E regulation may inform novel therapeutic approaches targeting skin barrier dysfunction and keratinization defects.