Corneodesmosin: Structure, Function and Involvement in Pathophysiology

Corneodesmosin (CDSN) was a protein specific to desmosomes, crucial for the integrity of the epidermis and hair follicles. It was secreted by granular keratinocytes and incorporated into desmosomes before transforming into corneodesmosomes. CDSN had adhesive properties due to its N-terminal glycine-rich domain and was proteolyzed as corneocytes migrated to the skin surface. Inactivation of CDSN in mice led to lethal epidermal barrier disruption and hair follicle degeneration, highlighting its essential role. CDSN was located on chromosome 6, within the major psoriasis susceptibility locus PSORS1. A rare autosomal dominant disease, hypotrichosis simplex of the scalp, was associated with nonsense mutations in CDSN, resulting in a truncated protein. The review detailed the discovery of CDSN and its structure-function relationship, emphasizing insights gained from mouse models and human diseases.