Cytokeratins comprise a diverse group of intermediate filament proteins that are expressed as pairs in both keratinized and non-keratinized epithelial tissue. Cytokeratins play a critical role in differentiation and tissue specialization and function to maintain the overall structural integrity of epithelial cells. Cytokeratin 9 is an unusually large, type I acidic cytokeratin that differentiates human plantar and palmar epidermal cells. Cytokeratin 9 localizes to the suprabasal layers as well as the upper epidermal layers such as the glandular ridges and interridges. The domains of cytokeratin 9 include a head, an α-helical coiled-coil-forming rod, and a tail; cytokeratin 9 shares significant homology with cytokeratin 10. Mutations in the cytokeratin 9 gene correlate with the development of epidermolytic palmoplantar keratoderma (EPPK), an autosomal dominant inherited skin disorder that is characterized by hyperkeratosis of the skin over the palms and soles.