LCE5A (late cornified envelope 5A) is a structural protein precursor of the cornified envelope in the stratum corneum, the outermost layer of epidermis 1. As a component of the terminal differentiation program, LCE5A expression is tightly regulated during normal skin barrier homeostasis and barrier repair responses 1. The protein functions through protein-binding interactions to assemble structural components of the cornified envelope 2. LCE5A expression is significantly downregulated in inflammatory skin diseases. In both atopic dermatitis and psoriasis lesions, LCE5A levels are substantially reduced compared to healthy controls, indicating compromised barrier function 2. Following experimental skin barrier disruption via tape stripping, LCE5A is rapidly downregulated at both mRNA and protein levels as part of the acute barrier damage response 1. In psoriasis specifically, LCE5A downregulation occurs within sebaceous gland compartments alongside keratinization pathway alterations 3. Clinically, reduced LCE5A expression serves as a biomarker of impaired skin barrier integrity in inflammatory dermatitis. Additionally, elevated LCE5A expression has been associated with unfavorable prognosis in lung adenocarcinoma, suggesting potential context-dependent roles beyond cutaneous biology 4. Overall, LCE5A represents a critical terminal differentiation marker reflecting barrier function status in skin diseases.