Carbonic anhydrases are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. Carbonic anhydrases are involved in various biological processes, including respiration, calcification, acid-base balance, bone resorption, as well as the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They have widespread tissue distribution and subcellular localization diversity.Carbonic anhydrase 14 (CA14) is a polypeptide composed of an extracellular N-terminal catalytic domain, a transmembrane domain, and a short intracellular C-terminal fragment with potential phosphorylation sites. CA14 is expressed on the cell bodies and axonal membranes of brain neurons, hepatocyte plasma membranes in the liver, and preferentially on the apical membrane of proximal tubules in the kidney. CA14 has the highest sequence similarity with another transmembrane CA isoform, CA12. However, they have different tissue-specific expression patterns and are thus likely to play different physiological roles. CA14 and CA4 can regulate the intracellular pH of hippocampal neurons by promoting chloride-bicarbonate exchange mediated by AE3.