The maintenance of pHe and pHi in the tumour mainly relies on some specific proton pumps and intracellular buffer systems.10,68,69 For instance, the balance of HCO3−/CO32− buffer system in tumour is administrated by carbonic anhydrase enzymes CA2, CA9 and CA12.12,70,71 Besides, the Na+/H+ buffer system is manipulated by Na+/H+ exchangers, such as SLC9A1.72 The regulation of pHe and pHi depends on the synergic effect of all of these pumps and buffer systems. The gene discussed is CA9; the disease is neoplasm.