However, this paradigm has been challenged in the last years as loss-of-function SCN5A mutations are found in a growing number of patients with dilated cardiomyopathy (Zaklyazminskaya and Dzemeshkevich, 2016; Asatryan, 2019), by the demonstration that Nav1.5 is part of a macromolecular complex which contains cytoskeleton proteins (Rook et al., 2012) and by the observation of dilatation and impairment in ventricular contractile function in patients carrying loss-of-function BrS SCN5A variants (van Hoorn et al., 2012). The gene discussed is SCN5A; the disease is dilated cardiomyopathy.