Cardiac calsequestrin (Casq2) is the major Ca2+ binding protein in the 
sarcoplasmic reticulum, which is the principle Ca2+ storage organelle of cardiac 
muscle. During the last decade, experimental studies have provided new concepts 
on the role of Casq2 in the regulation of cardiac muscle Ca2+ handling. 
Furthermore, mutations in the gene encoding for cardiac calsequestrin, CASQ2, 
cause a rare but severe form of catecholaminergic polymorphic ventricular 
tachycardia (CPVT). Here, we review the physiology of Casq2 in cardiac Ca2+ 
handling and discuss pathophysiological mechanisms that lead to CPVT caused by 
CASQ2 mutations. We also describe the clinical aspects of CPVT and provide an 
update of its contemporary clinical management.