[5][6][7] It is one of the 14 carbonic anhydrase isoforms found in humans and is a transmembrane dimeric metalloenzyme with an extracellular active site that facilitates acid secretion in the gastrointestinal tract.

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.

[17] The promoter region of the CA9 gene contains an HRE (hypoxia responsive element) where HIF-1 can bind, which allows hypoxic conditions to increase CA IX expression.

[22][11] Its overexpression in cancerous tissues compared to normal ones is due to hypoxic conditions in the tumor microenvironment caused by abnormal vasculature and subsequent transcriptional activation by HIF-1 binding.

[17] In clear cell renal carcinomas, CA IX shows high expression under normoxia due to a mutation in the VHL gene that normally negatively regulates HIF-1.

[23][24] CA IX plays a very significant role in tumor acidification as it has very high catalytic activity with the highest rate of proton transfer of the known CAs.

Girentuximab, an antibody that binds to CA IX, failed to improve disease-free as well as overall survival of patients with clear cell RCC in Phase III clinical trials.

[15] Coumarins serve as mechanism-based inhibitors that are hydrolyzed by the enzyme to form a cis-2-hydroxycinnamic acid derivative that then binds to the active site.