The authors searched PubMed/MEDLINE for English-language articles from 2005 to 2025 using combinations of the following terms: renal cell carcinoma, acidic TME, tumour acidosis, carbonic anhydrase IX/CA9, proton-sensing GPCRs, GPR65, GPR68, GPR4, immune evasion, immunotherapy resistance, and checkpoint inhibitors. Here, CA9 is linked to hereditary clear cell renal cell carcinoma.