IDH2 and central nervous system cancer: In addition to reducing affinity for isocitrate and losing its normal catalytic activity [134], mutant IDH1 or IDH2 also gained the function of catalyzing the reduction of α-KG to produce the (R) enantiomer of 2-hydroxyglutarate, (R)-2HG (also known as D-2HG), which accumulates in IDH1 or IDH2 mutated gliomas to millimolar concentrations [135] (Figure 2).