KRT8 is a type II keratin that functions as a structural component of intermediate filaments essential for epithelial integrity and cellular stress responses. KRT8 forms heteropolymeric filaments with KRT18 and KRT19, contributing to cytoskeletal organization and mechanical force transmission in epithelial tissues 1. Beyond structural roles, KRT8 marks transitional epithelial cell states during tissue regeneration and repair. During lung injury, airway and alveolar stem cells converge on a KRT8+ transitional state featuring senescence markers and p53/NFkB activation, which persists abnormally in human lung fibrosis 2. In early lung adenocarcinoma, KRT8+ alveolar intermediate cells display reduced differentiation, increased plasticity, and harbor KRAS mutations, serving as potential intermediates in malignant transformation 3. KRT8 dysregulation is particularly significant in pulmonary fibrosis pathogenesis. Genetic KRT8 variants associate with idiopathic pulmonary fibrosis (IPF) susceptibility, and keratin 8 regulates macrophage chemokine expression and recruitment, establishing profibrotic feedback loops 4. IL-11 signaling maintains aberrant KRT8+ basaloid cells in fibrotic lesions, blocking beneficial AT2-to-AT1 differentiation 5. In cancer, NAT10-mediated mRNA acetylation stabilizes KRT8 to promote epithelial-mesenchymal transition and metastatic progression 6. KRT8 expression thus marks pathological cellular states and represents a therapeutic target in fibrotic and neoplastic diseases.