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Carbonic anhydrases are a large family of zinc metalloenzymes that catalyze reversible hydration of carbon dioxide. They have a wide range of tissue distribution and subcellular localization diversity. Carbonic anhydrase 14 (CA14) is a polypeptide consisting of an extracellular n-terminal catalytic domain, a transmembrane region, and a short intracellular C-terminal fragment with potential phosphorylation sites. CA14 is expressed in the cell body and axon plasma membrane of brain neurons and hepatic cell plasma membrane of liver, and is preferentially expressed in the kidney, especially the proximal tubule apex membrane. CA14 has the highest sequence similarity to another transmembrane CA isomer, CA12. However, they have different tissue-specific expression patterns and may therefore play different physiological roles. CA14 and CA4 regulate intracellular pH of hippocampal neurons by promoting AE3-mediated Cl -- HCO3- exchange.