In PKP2 IVS10-1G>C knock-in mice, early AAV-PKP2 delivery at postnatal day 2 restored PKP2 expression, desmosomal protein levels (DSP, DSG2, JUP), and gap junction protein CX43, fully preventing ARVC phenotype and ensuring 100% survival up to 6 months. Late-stage administration at 4 weeks also significantly improved cardiac function, reduced fibrosis, normalized ECG (QRS duration), eliminated PVCs (0% vs. 60% in controls), and improved survival to 100% at 20 weeks vs. 20% in GFP controls. Rescue occurred even at advanced disease stages. The gene discussed is DSG2; the disease is arrhythmogenic right ventricular cardiomyopathy.