In silico: Arrhythmia suppression achieved with 1.4-fold CASQ2 overexpression for Class 1 RyR2 mutations and 1.8-fold for Class 2.In vivo: CASQ2 gene therapy completely prevented arrhythmias upon caffeine/epinephrine challenge (0/12 treated vs. 17/32 untreated mice; p = 0.0012), showing potent antiarrhythmic efficacy and validating CASQ2 overexpression as a novel therapeutic approach in CPVT1. The gene discussed is RYR2; the disease is cardiac arrhythmia.