IDH2 is a mitochondrial NADP(+)-dependent enzyme that catalyzes the conversion of isocitrate to α-ketoglutarate, playing a central role in intermediary metabolism and energy production 1. The enzyme contributes to generating NADPH as reductive potential in cellular processes 2 and may interact with the pyruvate dehydrogenase complex 1. IDH2 mutations occur in multiple malignancies, particularly gliomas and acute myeloid leukemia (AML). In gliomas, IDH2 mutations (affecting amino acid R172) are found in approximately 70% of WHO grade II-III astrocytomas and oligodendrogliomas, as well as secondary glioblastomas 1. Mutant IDH2 exhibits neomorphic activity, converting α-ketoglutarate to the oncometabolite 2-hydroxyglutarate (2-HG), which accumulates and disrupts α-ketoglutarate-dependent enzymes including epigenetic regulators 3. This leads to altered gene expression and blocked myeloid differentiation in AML 2. Clinically, IDH2 mutations serve as strong prognostic biomarkers; glioma patients with IDH2 mutations show significantly better overall and progression-free survival compared to wild-type tumors 4. IDH2 is also involved in chemoresistance mechanisms in urothelial carcinoma through metabolic reprogramming 5. Pharmacological IDH2 inhibitors, including vorasidenib, have demonstrated clinical efficacy, with vorasidenib approved for IDH-mutant glioma treatment 6.