The Na+/Ca2+ exchangers are a group of transmembrane proteins that regulate the transmembrane transport of Na+ and Ca2+, maintaining the balance of calcium ion concentration inside and outside the cell. The family members include various subtypes, structurally characterized by multiple transmembrane domains. They are localized in various cells and tissues, such as cardiomyocytes and neurons, participating in physiological processes like cellular signaling and muscle contraction. The activity of these exchangers is regulated by intracellular and extracellular ion concentrations and cellular signaling. Gene expression exhibits tissue specificity. Mutations or dysfunction are associated with health issues such as heart disease and neurological disorders, making them important targets for disease research and treatment.