In many cell types, the Ca2+ extrusion from the cytosol is available mainly via the Ca2+-ATPase and the Na+/Ca2+ exchanger (NCX) proteins, and, thereby, these systems play a critical role in maintaining, handling and modifying the dynamic changes in the cellular Ca2+ levels. Under most physiological conditions, NCX utilizes the electrochemical gradient for downhill movement of 3Na+ into the cell to mediate the uphill extrusion of 1Ca2+ from the cell, where during the transport cycle, the Na+ and Ca2+ ions are transported in separate steps through the NCX protein. NCX proteins play a key role in regulating the Ca2+ homeostasis in many cell types, and, thus, modulate the cardiac rate and contractile force, blood pressure, kidney Ca2+ reabsorption, neurotransmitter and hormones secretion, apoptosis, cellular proliferation, and ATP synthesis rates in mitochondria, among other roles.[1]