Cytokeratin 16 (CK16), also known as keratin 16, is a member of the large intermediate filament protein family that form the cytoskeleton. This family is subdivided into acidic (type I) and basic (type II) cytokeratins, but are obligatory heteropolymers, where expression of at least one member of each subfamily is required for filament formation. CK16 is classified as type I, pairing with type II cytokeratin 6. In normal tissues, CK16 is constitutively expressed at low levels in the palmar and plantar epidermis, tongue, oral mucosa, and hair follicles.

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, up regulation 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.