Calsequestrin is a high-capacity, moderate affinity, calcium-binding protein and thus acts as an internal calcium store in muscle. Calcium ions are bound by clusters of acidic residues at the protein surface, especially at the interface between subunits. Can bind around 60 Ca(2+) ions. Regulates the release of lumenal Ca(2+) via the calcium release channel RYR2; this plays an important role in triggering muscle contraction. Plays a role in excitation-contraction coupling in the heart and in regulating the rate of heart beats. Monomer, homodimer and homooligomer. Mostly monomeric in the absence of calcium. Forms higher oligomers in a calcium-dependent manner. Dimers associate to form tetramers, that then form linear homomer chains. Interacts with ASPH and TRDN (By similarity). This isoform of calsequestrin occurs in the sarcoplasmic reticulum's terminal cisternae luminal spaces of cardiac and slow skeletal muscle cells. Detected in heart (at protein level). Detected in heart. Phosphorylation in the C-terminus moderately increases calcium buffering capacity. N-glycosylated. Mutant mice are born at the expected Mendelian rate, are viable and display normal sarcoplasmic calcium release and normal heart function under basal conditions, but have a slower heart rate. Mutant mice are subject to polymorphic arrhythmia after exercise and to catecholaminergic ventricular arrhythmia, and their myocytes show increased Ca(2+) release in response to isoproterenol. Besides, the volume of the junctional sarcoplasmic reticulum is increased, and it seems to lack visible content. Belongs to the calsequestrin family.