LCE2B (late cornified envelope 2B) is a structural protein precursor that contributes to cornified envelope formation in the stratum corneum, the outermost layer of epidermis 1. As part of the late cornified envelope gene family, LCE2B participates in keratinocyte terminal differentiation and epidermal barrier function 2. During skin barrier repair following experimental disruption, LCE2B expression is significantly downregulated at both mRNA and protein levels, suggesting its role in maintaining normal barrier integrity 1. LCE2B has emerged as a disease-relevant gene in multiple conditions: it appears among the top genes involved in genetic cross-talk between periodontitis and hypothyroidism, playing a significant role in developmental processes and cell differentiation 3. In laryngeal squamous cell carcinoma, LCE2B is part of a six-gene expression signature associated with angiolymphatic invasion and poor survival outcomes, with high-risk patients showing significantly decreased overall and progression-free survival 4. Additionally, LCE2B is identified as a significantly mutated gene specifically in Black patients with esophageal adenocarcinoma, suggesting potential racial disparities in molecular mutation patterns relevant to cancer development 5. These findings indicate LCE2B functions beyond simple structural roles, connecting cornification to immune, inflammatory, and malignant disease processes.