RYR2 and catecholaminergic polymorphic ventricular tachycardia: Remarkably, mutant RyR2 channels, harboring the CPVT-linked single-point mutation RyR2R2474S (RyR2RS), show increased open probability (Po) when PKA-phosphorylated [7,12,13], which alters local control of Ca2+ signals at RyR2 clusters, causing increased diastolic Ca2+ leak from the SR in CPVT cardiomyocytes (CMs) challenged with β-adrenergic (β-AR) agonists [7,14].