KRT81 is a hair-specific type II keratin that functions as a structural intermediate filament protein with cysteine-rich terminal domains enabling extensive disulfide cross-linking 1. Beyond its classical role in hair cortex differentiation, KRT81 is aberrantly expressed in multiple cancer contexts, where it promotes malignant phenotypes through distinct mechanisms. In breast cancer cells, KRT81 expression correlates with increased migration and invasion via upregulation of matrix metallopeptidase 9 (MMP9) 2. In colorectal cancer, KRT81 acts as a protein scaffold for ezrin, facilitating filopodia formation and metastatic dissemination; combined inhibition of KRT81 and ezrin shows enhanced suppression of invasion 3. In pancreatic ductal adenocarcinoma, KRT81 expression status—assessed by immunohistochemistry alongside HNF1A—stratifies patients into prognostically and predictively distinct subtypes with differential responses to gemcitabine-based and erlotinib-based chemotherapy 45. In triple-negative breast cancer, higher KRT81 expression predicts worse outcomes and correlates with suppression of CD8+ T-cell infiltration and increased expression of the immune checkpoint molecule CD276 6. Pathogenic variants in related hair keratins (KRT31, KRT81, KRT83, KRT86) cause monilethrix, an inherited hair-shaft disorder characterized by periodic thinning and fragility 78. A microRNA-responsive SNP in KRT81 (rs3660 GG genotype) independently predicts shorter survival in non-Hodgkin's lymphoma 9.