Abstract
Mitochondrial calcium homeostasis is an important regulator of bioenergetics, redox balance and cell survival. This review discusses the structure, regulation and pathophysiological significance of the mitochondrial Na⁺/Ca²⁺ exchanger NCLX, encoded by the SLC8B1 gene. Particular attention is paid to the role of NCLX in Ca²⁺ efflux from the mitochondrial matrix, integration of Na⁺–Ca²⁺–ROS signaling, and cellular responses to metabolic stress, hypoxia and mitochondrial injury. The available data indicate that NCLX dysfunction contributes to the pathophysiology of neurodegenerative, cardiovascular, metabolic, inflammatory and neoplastic diseases. However, the function of this transporter strongly depends on cell type, duration of stress and the degree of mitochondrial Ca²⁺ overload. Therefore, NCLX should be considered a regulator of mitochondrial function whose diagnostic, prognostic and therapeutic relevance requires further validation in experimental and clinical studies.