Plasma membrane Ca transport ATPases (PMCA1-4, ATP2B1-4) are responsible for removing excess Ca from the cell in order to keep the cytosolic Ca ion concentration at the low level essential for normal cell function. While these pumps take care of cellular Ca homeostasis they also change the duration and amplitude of the Ca signal and can create Ca gradients across the cell. This is accomplished by generating more than twenty PMCA variants each having the character - fast or slow response, long or short memory, distinct interaction partners and localization signals - that meets the specific needs of the particular cell-type in which they are expressed. It has become apparent that these pumps are essential to normal tissue development and their malfunctioning can be linked to different pathological conditions such as certain types of neurodegenerative and heart diseases, hearing loss and cancer. In this chapter we summarize the complexity of PMCA regulation and function under normal and pathological conditions with particular attention to recent developments of the field.
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