Both the membrane transporters and CAIX/CAXII are upregulated via HIF1α and form a functional complex, a so called “Metabolon”, which facilitates extrusion of acidic metabolites, such as lactate, in highly hypoxic and CO2 in moderately hypoxic tumor tissue and ensures uptake of bicarbonate (HCO3−), which is used to buffer intracellular protons [14,15,16]. The gene discussed is CA9; the disease is neoplasm.