KRT76 (keratin 76) is an intermediate filament protein that plays essential roles in epithelial differentiation and barrier function. The protein is expressed in differentiated epithelial layers of stratified epithelia including skin, oral cavity, and squamous stomach 1. KRT76 is required for maintaining tight junction function and skin barrier integrity through direct interaction with claudin-1 (CLDN1), helping to correctly position CLDN1 in tight junctions 2. Loss of KRT76 in mice causes severe skin phenotypes including neonatal flaking, hyperpigmentation, inflammation, impaired wound healing, and death before 12 weeks due to functionally defective tight junctions 2. Beyond structural functions, KRT76 has important immunomodulatory roles, as genetic ablation leads to systemic inflammation with increased regulatory T cells, pro-inflammatory cytokines, and enhanced susceptibility to carcinogen-induced tumors in tongue and stomach 1. In human cancers, KRT76 downregulation correlates with poor prognosis in oral squamous cell carcinoma and is associated with increased tumor-infiltrating regulatory T cells 13. The protein's expression is regulated by DNA methylation patterns, with hypermethylation contributing to its downregulation in disease states 4. These findings establish KRT76 as a multifunctional protein linking cytoskeletal integrity, barrier function, and immune regulation.