SLC4A8 encodes the sodium-driven chloride/bicarbonate exchanger (NDCBE), a member of the SLC4 family of cation-coupled bicarbonate transporters 1. NDCBE mediates electroneutral sodium- and carbonate-dependent chloride-bicarbonate exchange with a Na+:HCO3- stoichiometry of 2:1 2. The gene produces multiple splice variants (NDCBE-A, -B, -C, -D) with distinct functional properties, where C-terminal variations affect functional expression levels 2. In the nervous system, NDCBE functions as a major intracellular pH regulator in hippocampal pyramidal neurons and other CNS neurons, with expression localized to neuronal cell bodies and processes 3. In the kidney, SLC4A8 mediates sodium reabsorption in the renal cortical collecting duct through collaboration with pendrin in intercalated cells 4. Importantly, NDCBE mediates thiazide-sensitive Na+ reabsorption in cortical collecting ducts via apical sodium uptake into intercalated cells, identifying a novel pathway distinct from ENaC-dependent mechanisms 5. Genetic alterations in SLC4A8 have been associated with cancer prognosis; the gene was identified as part of an m6A-related prognostic signature for ovarian cancer 6. The cryo-EM structure of NDCBE's outward-facing conformation provides mechanistic insights into its transport mode determination within the SLC4 family 7.