The increase in diastolic Ca2+ leak is potentially a pathological substrate for the induction of arrhythmias, as the released Ca2+ from the SR can diffuse to neighboring RyR2 clusters to induce pro-arrhythmogenic Ca2+ events that, together with automatic contractions, ultimately trigger ventricular arrhythmias. The gene discussed is RYR2; the disease is cardiac arrhythmia.