Figure 4.

Corneodesmosome defects in skin conditions associated with epidermal barrier dysfunction. Desquamation is determined by de novo synthesis and degradation of corneodesmosomal proteins. Mutations in GDSN encoding corneodesmosin and DSG1 encoding desmoglein 1 can cause an inflammatory type of peeling skin syndrome and SAM syndrome (severe skin dermatitis, multiple allergies, and metabolic wasting), which is another inflammatory type of peeling skin syndrome, respectively. Degradation of corneodesmosomal proteins depends on the sum of activities from proteases, including kallikrein-related peptidases (KLKs) and protease inhibitors including lymphoepithelial-Kazal-type 5 inhibitor (LEKTI). Experimental conditions, such as retinoic acid (RA) application, soap and detergent washing, and long-term corticosteroid (CS) application, could also accelerate desquamation mainly by increased production of KLKs.