Cytokeratin 16 (CK16) is a protein that in humans is encoded by the KRT16 gene. Cytokeratin 16 is a type I cytokeratin. It is paired with cytokeratin 6 in a number of epithelial tissues, including nail bed, esophagus, tongue, and hair follicles. Mutations in the gene encoding this protein are associated with the genetic skin disorders pachyonychia congenita, non-epidermolytic palmoplantar keratoderma and unilateral palmoplantar verrucous nevus.

Studies have proposed a modulatory role of CK16 in cell proliferation, suggesting its utility as a marker for proliferation. Rapid induction of CK16 expression near the edge of wounds, upregulation in response to epidermal growth factor stimulus, and overexpression in hyperproliferative disorders, including psoriasis and chronic contact dermatitis, support this assertion. In psoriasis, the severity of disease is correlated with the amount of CK16. Additionally, CK16 expression has been described in neoplasms of multiple tissues. Progressive CK16 abundance and intensity were observed with increased grade of severity of cervical intraepithelial neoplasia lesions. Furthermore, 10% of invasive carcinomas were diffusely or focally positive. In keratocystic odontogenic tumors, CK16 was observed in 79% of cases. These observations support CK16 as a marker of hyperproliferation.