The plasma membrane pump is a primary means by which Ca2+ is exported from all kinds of mammalian cells. This review focuses on currently active areas of research on this pump, including the topology of the pump, the regulatory domains (including the calmodulin-binding and lipid-binding domains), other means of regulation, its involvement in transcellular Ca2+ transport and its heterologous expression for site-directed mutagenesis studies. The role of the pump in cellular function and disease is assessed, including its localization in different cells and the possible mechanism by which the pump is inhibited in uncontrolled diabetes.