KRT6B (keratin 6B) is a structural intermediate filament protein that functions as a key component of the epidermis and cytoskeleton 1. As a wound-activated protein, KRT6B is significantly upregulated during skin epithelialization and keratinocyte proliferation, with eIF6 negatively regulating this process 1. Beyond its canonical role in keratinization and skin development, KRT6B has emerged as a multifunctional oncogenic mediator across multiple cancer types. In lung adenocarcinoma, KRT6B functions as a central hub gene within an immune-related prognostic signature, with overexpression promoting tumor growth in vitro and in vivo 2. In bladder cancer, KRT6B is encapsulated in tumor-derived exosomes and promotes invasion and metastasis by inducing epithelial-mesenchymal transition (EMT) while simultaneously regulating the immune microenvironment 3. KRT6B expression correlates with advanced disease stage, grade, and metastatic status in bladder cancer 3. In hepatocellular carcinoma, KRT6B mediates Notch1 signaling to promote cell proliferation and suppress apoptosis 4. Additionally, KRT6B is upregulated in metastatic urothelial carcinoma and correlates with worse clinical outcomes and higher tumor grade 5. KRT6B's pathogenic role is further supported by its involvement in pterygium and meibomian gland dysfunction through keratinization pathways 6, and by evidence that PDE3B-mediated KRT6B downregulation enhances therapeutic sensitivity in bladder cancer 7. These findings establish KRT6B as a promising diagnostic biomarker and therapeutic target across multiple malignancies.