Mutant of IDH1 and IDH2 enzymes have a gain the function of catalyzing the reduction of α-KG to its (R)-enantiomer of 2-hydroxyglutarate (2HG), which accumulates to exceedingly high levels in patients with glioma, acute myeloid leukemia, esophageal squamous cell carcinoma (180–183) thus, 2HG levels being used as a biomarker for IDH mutation in these cancers (184). Here, IDH2 is linked to central nervous system cancer.