IDH2 and neoplasm: Most common tumor-associated IDH1/2 mutations are located in key arginine residues (R132 for IDH1, R140, or R172 for IDH2) for the recognition of the substrate [9,10], and lead to a neomorphic gain of function enzyme with a markedly decreased affinity for isocitrate, capable instead of catalyzing the conversion of α-KG into 2-hydroxyglutarate (2-HG) in an NADPH-dependent manner.