Cardiac Calsequestrin: The New Kid on the Block in Arrhythmias

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare inherited disease characterized by physical or emotional stress-induced ventricular arrhythmias in the absence of any structural heart disease or QT prolongation. Thus far, mutations in genes encoding the sarcoplasmic reticulum Ca²⁺ release channel (RYR2) and the sarcoplasmic reticulum Ca²⁺ binding protein cardiac calsequestrin (CASQ2) have been identified in CPVT patients. Here, we review the role of cardiac calsequestrin in health and disease, with a particular focus on how calsequestrin deficiency can cause arrhythmia susceptibility. Clinical implications and a promising new drug therapy for CPVT are discussed.