Carbonic anhydrases IV and XV.

Carbonic anhydrases (CAs) IV and XV are glycosylphosphatidylinositol (GPI)-anchored membrane-associated enzymes involved in the regulation of pH and ion homeostasis. This review summarizes current knowledge on their structure, post-translational modifications, tissue distribution, physiological roles, and inhibition profiles. CA IV is widely expressed across multiple tissues, including kidney, lung, brain, and reproductive organs, where it participates in ion transport processes and forms functional and physical interactions with ion transporters. In contrast, CA XV displays a highly restricted expression pattern, primarily localized to specific nephron segments in the kidney, and is absent in humans. Comparative analyses highlight both shared structural features and distinct functional specializations between these isozymes. In addition, CA IV has been implicated in human disease, particularly retinitis pigmentosa, whereas CA XV remains less explored due to its limited clinical relevance. Understanding these enzymes provides insight into membrane-associated CA biology and their potential as pharmacological targets.