More direct treatment strategies targeting the RyR2 macromolecular complex that have been successfully tested using animal models include (1) pharmacological inhibition of RyR2 (dantrolene [44], flecainide [81], JTV-519 [48, 83]); (2) overexpression of WT form of accessory protein (i.e., CASQ) to reduce impact of a recessive CPVT mutation [52]; (3) gene editing-mediated disruption or siRNA-mediated suppression of a dominant CPVT mutation disease-causing allele [8, 62]; and (4) expression of exogenous plant form of regulatory protein CALM with enhanced ability to stabilize RyR2 [50]. This evidence concerns the gene CALM2 and catecholaminergic polymorphic ventricular tachycardia.