Keratins are cytoplasmic intermediate filament proteins expressed by epithelial cells. The mitotically active basal layers of most stratified squamous epithelia express 10% to 30% of their total protein as keratin. The two keratins specifically expressed in these cells are the type II keratin CK5 and its corresponding partner, type I keratin CK14, both of which are essential for the formation of 8-nm filaments. CK5 and calretinin have been useful in different studies as immunohistochemical markers suggestive of mesothelioma, and their expression is analyzed for the histological differential diagnosis with adenocarcinomas, especially when confronting with metastatic tumors of unknown origin. CK5 labels myoepithelial cells of breast and prostate basal cells. A cocktail of CK5, CK14 and p63, has been used as sensitive and specific basal cell marker of basal-like phenotype of breast carcinoma and to differentiate benign prostate from prostate cancer. Loss-of-function mutations in the keratin 5 gene (KRT5) affected family members and in six unrelated patients with Dowling-Degos disease (DDD), an autosomal dominant genodermatosis. This suggests a crucial role for keratins in the organization of cell adhesion, melanosome uptake, organelle transport, and nuclear anchorage.