Corneodesmosin is a protein found in corneodesmosomes, which localize to human epidermis and other cornified squamous epithelia. During maturation of the cornified layers, the protein undergoes a series of cleavages, which are thought to be required for desquamation. The gene is located in the major histocompatibility complex (MHC) class I region on chromosome 6.

Corneodesmosomes are intercellular structures that are involved in desquamation, the shedding of superficial corneocytes from the skin surface. Corneocytes are anucleated cells derived from keratinocytes during the late stages of terminal differentiation of cornified squamous epithelia such as the epidermis.