RYR1 and catecholaminergic polymorphic ventricular tachycardia: Other activators and agonists independent of Ca2+ could chronically activate RyRs thereby enhancing pathologic Ca2+ leak, which is associated with gain-of-function RyR diseases such as Malignant Hyperthermia and Catecholaminergic Polymorphic Ventricular Tachycardia.