Mitochondrial sodium/calcium antiporter that mediates sodium-dependent calcium efflux from mitochondrion, by mediating the exchange of 3 sodium ions per 1 calcium ion (PubMed:20018762, PubMed:28445457). Plays a central role in mitochondrial calcium homeostasis by mediating mitochondrial calcium extrusion: calcium efflux is essential for mitochondrial function and cell survival, notably in cardiomyocytes (PubMed:24067497, PubMed:28445457). Regulates rates of glucose-dependent insulin secretion in pancreatic beta-cells during the first phase of insulin secretion: acts by mediating efflux of calcium from mitochondrion, thereby affecting cytoplasmic calcium responses (By similarity). Required for store-operated Ca(2+) entry (SOCE) and Ca(2+) release-activated Ca(2+) (CRAC) channel regulation: sodium transport by SLC8B1 leads to promote calcium-shuttling that modulates mitochondrial redox status, thereby regulating SOCE activity (By similarity). Involved in B-lymphocyte chemotaxis (PubMed:27328625). Able to transport Ca(2+) in exchange of either Li(+) or Na(+), explaining how Li(+) catalyzes Ca(2+) exchange (By similarity). In contrast to other members of the family its function is independent of K(+) (By similarity). Ca(2+)(in) + 3 Na(+)(out) = Ca(2+)(out) + 3 Na(+)(in) Inhibited by the sodium/calcium exchanger inhibitor CGP-37157 (PubMed:28445457). Strongly inhibited by zinc (By similarity). Mainly localizes to mitochondrion inner membrane (PubMed:20018762). Ubiquitously expressed. Expressed in dental tissues. Phosphorylation at Ser-258 by PKA prevents calcium overload. Conditional deletion in adult hearts causes sudden death in 87% of the mice. Hearts show substantial cardiac remodeling, including an increase in heart mass and correlative change in cardiomyocyte cross-sectional area, as well as a significant increase in cardiac fibrosis. Defects are probably due to mitochondrial calcium overload leading to increased generation of superoxide and necrotic cell death. Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19) family. SLC24A subfamily. Isoform 1 was reported to not have cation exchanger activity (PubMed:12080145). However, such result is unclear. Isoform 1 and isoform 2 were reported to localize to the endoplasmic reticulum membrane and cell membrane, respectively (PubMed:14625281). This result is however not supported by other studies that report localization to the mitochondrial membrane (PubMed:20018762, PubMed:24067497).