The open probability of RyR2 in response to variations in cytoplasmic Ca2+ concentration is regulated by both Ca2+ free (apo-) and Ca2+/CaM (Balshaw et al., 2001, 2002; Brohus et al., 2019; Sigalas et al., 2009; Walweel et al., 2017; Xu and Meissner, 2004; Yamaguchi et al., 2007, 2003; Yang et al., 2014); however, the effect of CPVT-associated CaM mutations on CaM–RyR2 function remains unclear. The gene discussed is RYR2; the disease is catecholaminergic polymorphic ventricular tachycardia.