Our preclinical results demonstrated that AAV9-based PKP2 gene replacement approach can offer significant survival benefit in repairing cellular structures of desmosome, GJs, and Ca2+-handling system, improving cardiac function, reducing PVC frequency and occurrences of NSVT, and preventing adverse fibrotic remodeling in a dose-dependent fashion in a cardiac-specific Pkp2 knock-out mouse model of ARVC. The gene discussed is PKP2; the disease is arrhythmogenic right ventricular cardiomyopathy.