The structural integrity of the skin is maintained by cell-cell adhesion mediated by desmosomes, which has desmoglein as an important transmembrane component. Now it is known that desmoglein is targeted by two skin diseases, pemphigus and staphylococcal scalded skin syndrome (SSSS). Pemphigus is a group of autoimmune blistering diseases of the skin and mucous membranes that are caused by IgG autoantibodies against desmoglein. Patients with pemphigus vulgaris and pemphigus foliaceus have IgG autoantibodies against desmoglein 3 and desmoglein 1, respectively. Even complex clinical variations of pemphigus are logically explained by desmoglein compensation theory. SSSS and its localized form, bullous impetigo, are caused by exfoliative toxin (ET) produced by S. aureus. Now it is Known that all three serotypes of ET, ETA, ETB, and ETD specifically recognize desmoglein 1 and digest desmoglein1 once after glutamic acid residue 381 between extracellular domains 3 and 4.