Peeling Skin Disorders: A Paradigm for Skin Desquamation

Epidermal desquamation is the highly regulated process of invisible shedding of corneocytes from the outermost layers of the stratum corneum. This occurs through the interplay between proteases and their inhibitors that control the degradation of corneodesmosomes. Skin peeling refers to exaggerated visible superficial desquamation and can occur in inherited and acquired conditions. The illumination of the molecular basis of genetic disorders with skin peeling sheds light on the biological mechanisms of epidermal desquamation and skin barrier homeostasis. Proteins that are mutated in peeling skin disorders are components of corneodesmosomes (CDSN, DSG1) or protease inhibitors (LEKTI, CSTA, CAST, or SERPIN8). FLG2 emerged as a new player that regulates epidermal desquamation, as demonstrated by the phenotype observed in patients reported by 2 independent groups.