Studies in a transgenic mouse model of ARVC expressing a DSG2-N266S mutation suggested that cardiomyocyte death (necrosis) may be an initiating factor to this inflammatory response (Pilichou et al. 2009); however, the triggers and cause-effect relationship remains unexplained and an intense area of investigation. Here, DSG2 is linked to arrhythmogenic right ventricular cardiomyopathy.