Isocitrate dehydrogenases 1 and 2 (IDH1,2), the key Krebs cycle enzymes that generate NADPH reducing equivalents, undergo heterozygous mutations in >70% of low- to mid-grade gliomas and ~20% of acute myeloid leukemias (AMLs) and gain an unusual new activity of reducing the α-ketoglutarate (α-KG) to D-2 hydroxyglutarate (D-2HG) in a NADPH-consuming reaction. Here, IDH1 is linked to central nervous system cancer.