KRT80 is a type II intermediate filament protein widely expressed in epithelial tissues that serves as a structural component of the cytoskeleton 1. As a keratin family member, KRT80 contributes to mechanical cell cushioning, organelle positioning, and cytoskeletal organization 1. Unlike typical epithelial keratins, KRT80 is structurally more similar to hair keratins despite broad epithelial expression 1. In cancer pathophysiology, KRT80 expression is significantly upregulated across multiple malignancies including esophageal, gastric, and lung adenocarcinoma 234. Mechanistically, KRT80 promotes cancer cell proliferation, migration, and invasion while enhancing chemoresistance through lipid droplet assembly and ACC1/ACLY-mediated lipogenesis 2. In glioblastoma, KRT80 is regulated by RNF8-mediated ubiquitination and activates glycolytic pathways to drive tumor progression 5. Elevated KRT80 expression correlates with poor prognosis, advanced tumor stage, and reduced survival in multiple cancer types 34. Notably, in head and neck squamous carcinoma, KRT80 functions as a tumor suppressor regulated by the lncRNA HNSCAT1 6, contrasting with its oncogenic role in other malignancies. KRT80 serves as a diagnostic biomarker for cancer tissues, though its prognostic significance varies by cancer type 7.