Plasma membrane-type Ca2+-ATPases (PMCAs) mediate the export of bivalent calcium ions from eukaryotic cells. As members of the P class of ion-motive ATPases, PMCAs are a functionally diverse group of proteins that are derived from alternatively spliced transcripts originating from four distinct genes, PMCA1, 2, 3, and 4. The expression of different PMCA isoforms and splice variants is regulated in a developmental, tissue- and cell type-specific manner, and with respect to the physiological needs of specific cell and tissue types. Spatial and temporal rates of resting intracellular Ca2+ concentrations and Ca2+ signaling in eukaryotic cells are dependent on the array of PMCA isoforms that are expressed in concert with the rate of Ca2+ export. The human PMCA2 gene is located on chromosome 3, and antibodies directed against PMCA2 detect three proteins in brain and heart. Homozygous null mutations in the mouse gene result in deafwaddler mice, which are characterized by having a hesitant, wobbly gait, displaying head bobbing, and are deaf.