Function, regulation and physiological role of the mitochondrial Na + /Ca 2+ exchanger, NCLX

•NCLX is essential for cardiac survival, and knockout of NCLX leads to heart failure.•The general catalytic core of NCLX is shared by other Na+/Ca2+ exchangers, but unique residues confer its Li+ selectivity.•NCLX activity is regulated by phosphorylation in its regulatory domain and by changes in cytosolic Na+.•NCLX is linked to physiological activities, ranging from pain sensation to insulin secretion.•Crosstalk of NCLX with cell membrane channels, such as Orai1, LTCC and TRPV1 controls their activity.