The hallmark intraepidermal acantholysis that histologically characterizes PV is linked to the action of autoantibodies targeting critical desmosomal constituents—desmoglein 3 (Dsg3), and in many cases also desmoglein 1 (Dsg1)—, and potentially other non-Dsg targets (7–10) that are ultimately integral to cellular adhesion in the epidermis (11). The gene discussed is DSG3; the disease is acquired polycythemia vera.