Carbonic anhydrases (CAs) are a large family of zinc metalloenzymes that catalyze the reversible hydration of carbon dioxide. They participate in a variety of biological processes, including respiration, calcification, acid-base balance, bone resorption, and the formation of aqueous humor, cerebrospinal fluid, saliva, and gastric acid. They show extensive diversity in tissue distribution and in their subcellular localization. Carbonic anhydrases XIV (CA14) is a polypeptide consisting of an extracellular N-terminal catalytic domain, a membrane-spanning segment and a short intracellular C-terminal segment with several potential phosphorylation sites. It is expressed in the brain on plasma membranes of neuronal bodies and axons, in the liver on the plasma membranes of hepatocytes, and in the kidney preferentially on the apical membranes of proximal tubules. CA14 shares highest sequence similarity with the other transmembrane CA isoform, CA 12. However, they have different patterns of tissue-specific expression and thus may play different physiologic roles. CA14, together with CA4, play important roles in the regulation of intracellular pH in hippocampal neurons by facilitating AE3-mediated Cl- – HCO3- exchange.