Desmoglein 1 is the target antigen and probably the initiating immunogen of the autoantibody response in pemphigus foliaceus (PF), a blistering autoimmune skin disease. We previously showed that the desmoglein 1 gene (DSG1) is polymorphic and that one of its variants is associated with the sporadic form of PF observed in France. Herewith, we report, based on a case-control analysis, that the same DSG1 polymorphism participates in susceptibility to the endemic form of PF seen in Tunisia and, thus, show that common genetic factors govern the breakage of tolerance to desmoglein 1 in different epidemiological and environmental situations.