PKP2 and Arrhythmogenic right ventricular dysplasia: As human patients with ARVC are heterozygous for the PKP2 IVS10-1G>C mutation, our data also contribute to the growing evidence that a two-hit hypothesis (additional pathogenic stimulus) is central to elicit rapid ARVC pathogenesis by way of an additional genetic (a second desmosomal mutation or homozygous mutation) or physiological (for example, exercise stress) hit, especially in mouse settings8,24,40.