Calsequestrin (CASQ) is a Ca2+-binding protein present primarily in junctional sarcoplasmic reticulum of skeletal and cardiac muscle; the cardiac form (CASQ2) is encoded by a separate gene. The primary role of CASQ2 is buffering of the sarcoplasmic reticulum Ca2+ ions,but another role for CASQ2 has emerged recently: CASQ2 regulates the open probability of ryanodine receptor 2 (RyR2). Mutations in CASQ2 cause stress-induced polymorphic ventricular tachycardia,also referred to as catecholaminergic polymorphic ventricular tachycardia 2 (CPVT2),a disease characterized by bidirectional ventricular tachycardia that may lead to cardiac arrest.