These findings help to explain why autoantibodies against Dsg3 and Dsg1 were observed to cause different sets of signaling responses (48) and led us to propose that the different clinical phenotypes of pemphigus with respect to mucosal and skin involvement, as well as suprabasal versus superficial epidermal blistering, may at least in part be caused by the different signaling profiles observed in PV and PF (22). The gene discussed is DSG3; the disease is pemphigus.