KRT15 is a type I intermediate filament protein that functions as a structural component of the epithelial cytoskeleton, playing critical roles in maintaining cellular stability and organizing the intermediate filament network 1. In normal tissues, KRT15 marks quiescent stem/progenitor cell populations in basal epithelial layers, including those of the esophagus 2, and is expressed in club cells and basal cells during lung regeneration 3. KRT15 expression increases during epithelial differentiation of mesenchymal stem cells, alongside other keratin markers 4. Clinically, KRT15 dysregulation is associated with multiple cancer types. In colorectal cancer, KRT15 overexpression promotes cell migration and invasion through β-catenin/MMP-7 signaling and predicts poor prognosis [PMID:35477819; 52]. In breast cancer, reduced KRT15 expression discriminates invasive from in situ disease and correlates with tumor grade and proliferation markers 6. In head and neck squamous cell carcinoma, KRT15-high tumor cells of HPV-positive origin secrete CCL20, promoting tertiary lymphoid structure formation and enhancing immunotherapy response 7. In gastric cancer, aberrant KRT15 methylation with downregulation associates with poor prognosis 8. These findings establish KRT15 as both a developmental marker of epithelial stem cells and a prognostic biomarker with therapeutic potential.