KRT4 (keratin 4) is a structural protein located on chromosome 12.2-q12 1 that functions as a component of intermediate filaments in the epithelial cytoskeleton, particularly in oral mucosa and esophageal tissue. As a differentiation marker, KRT4 expression is associated with epithelial maturation and is preferentially expressed in differentiated layers of normal tissues 2. Mechanistically, KRT4 suppresses proliferation and promotes differentiation in epithelial cells. In oral squamous cell carcinoma (OSCC), KRT4 is downregulated through m6A methylation of exon-intron boundaries, which prevents normal pre-mRNA splicing and reduces DGCR8 binding 3. KRT4 also functions as a tumor suppressor: its overexpression restrains OSCC cell proliferation and viability while facilitating apoptosis 4, and high KRT4 expression predicts favorable prognosis in esophageal cancer patients receiving chemoradiotherapy 2. Clinically, KRT4 mutations cause white sponge nevus (WSN), an autosomal dominant disorder characterized by thickened, spongy oral mucosa with abnormal keratinization 56. The E520K mutation leads to epithelial dysfunction with increased hyalocytes and altered tonofilament organization. KRT4 represents a potential therapeutic target for oral cancer treatment and a candidate for gene-based diagnosis and therapy in keratin-associated diseases.