Strict spatiotemporal control of [Ca2+]i dynamics is crucial for normal cardiomyocyte function, and recent evidence demonstrated that Cx43 HC opening triggers disturbed [Ca2+]i dynamics in a plakophilin-2–knockout (PKP2-KO) mouse model of arrhythmogenic right ventricular cardiomyopathy (ARVC) (119). The gene discussed is PKP2; the disease is arrhythmogenic right ventricular cardiomyopathy.