As an example of pleiotropic genes, we are focusing our review on plakophilin-2 (PKP2) coded by the gene Pkp2, whose pathogenic role has been recently recognized in different inherited cardiac arrhythmias syndromes, ranging from Arrhythmogenic Cardiomyopathy (ACM or ARVC), Brugada Syndrome (BrS), idiopathic ventricular fibrillation, hypertrophic cardiomyopathy (HCM), and dilated cardiomyopathy (DCM). Here, PKP2 is linked to familial dilated cardiomyopathy.