LCE6A (late cornified envelope 6A) is a structural protein precursor that plays a critical role in forming the cornified envelope (CE) of the stratum corneum, the outermost barrier layer of the epidermis 1. As a member of the Late Cornified Envelope protein family, LCE6A is expressed late during epidermal differentiation and functions as a substrate for transglutaminases, which covalently crosslink LCE6A to other CE components to strengthen barrier mechanical resistance 1. This crosslinking capability has been leveraged to develop LCE6A-derived biomimetic peptides that reinforce the cornified envelope and protect skin from barrier disruption, aging-related damage, and loss of skin firmness 1. Clinically, altered LCE6A expression is associated with multiple pathological conditions: it is significantly downregulated in chr1 periodontitis gingival tissues 2, and differential expression of LCE6A has been identified as a potential biomarker in head and neck squamous cell carcinoma (HNSCC), where changes in its expression correlate with decreased patient survival 3. These findings underscore LCE6A's importance in epithelial barrier homeostasis and its potential value as both a therapeutic target and diagnostic marker in inflammatory and neoplastic diseases.