CA12 (carbonic anhydrase 12) is a transmembrane zinc-binding enzyme that catalyzes the reversible hydration of carbon dioxide 1, playing critical roles in pH regulation and ion homeostasis across multiple tissues. Mechanistically, CA12 functions as part of bicarbonate buffering systems in hypoxic tissues, where its expression is regulated by the PHD/HIF-1 axis 2. Under hypoxia, HIF-1 orchestrates CA12-dependent bicarbonate buffering to maintain intracellular pH and prevent metabolic dysfunction 3. CA12 is prominently expressed in the non-pigmented ciliary epithelium, where it influences aqueous humor production 1, and in the nucleus pulposus, where decreased expression contributes to degenerative disc disease progression by reducing extracellular matrix synthesis 2. In cancer contexts, CA12 shows paradoxical roles: high CA12 expression associates with improved breast cancer prognosis 4, yet CA12 inhibition protects cardiomyocytes against doxorubicin cardiotoxicity by suppressing glycolytic activation 5, and CA12 knockdown enhances chemotherapy sensitivity in breast cancer cells 6. Recently, IL-1β-induced CA12 promotes chondrocyte apoptosis and osteoarthritis progression through m6A-dependent mRNA stabilization 7. CA12 is also a VDR target gene in intestinal homeostasis 8. The isolated hyperchlorhidrosis association suggests CA12's role in chloride ion regulation.