ATP dependent calcium pumps are responsible, in part, for the maintenance of low cytoplasmic free calcium concentrations. The ATP pumps that reside in intracellular organelles are encoded by a family of structurally related enzymes, termed the sarcoplasmic or endoplasmic reticulum calcium (SERCA) ATPases. The sarcoplasmic reticulum of striated muscle is a specialized intracellular membrane system that plays a critical role in the contraction and relaxation of muscle. The SERCAs mediate Ca2+ uptake into intracellular stores. SERCA-mediated Ca2+ uptake induces and maintains muscular relaxation. The SERCA1 gene is exclusively expressed in type II (fast) skeletal muscle. The SERCA2 gene is subject to tissue-dependent processing which is responsible for the generation of the SERCA2a muscle-specific form expressed in type I (slow) skeletal, cardiac and smooth muscle, and the SERCA2b isoform expressed in all cell types. The SERCA3 gene is not as well characterized and is found in non-muscle cells. SERCA2 plays an important part in regulating cardiac contractile function. SERCA3 is an isoform expressed in several cell types including platelets, lymphoid cells and mast cells. SERCA1, SERCA2 and SERCA3 all undergo alternative splicing.