Isocitrate dehydrogenase(IDH)is a kind of crucial enzyme family in tricarboxylic acid(TCA)cycle,which convents socitric acid to α-ketoglutarate(α-KG)in mitochondria.The clinical data have shown that the point mutations in the activesite arginine residues of IDH(IDH1/R132,IDH2/R140,and IDH2/R172)occur frequently in a variety of cancers,including acute myeloid leukemia(AML),brain tumors,and holangiocarcinomas.The IDH mutants catalyze α-KG to oncometabolite 2-hydroxyglutarate(2-HG),which dysregulates a set of α-KG-dependent dioxygenases.The recent studies of IDH1/2 have made a series of progress in clinical trials: 1)Next Generation Sequencing has been used to detect all types of mutation in either IDH1 or IDH2;2)IDH1/2 mutation status was used to distinguish intracranial chondrosarcomas from chordomas;3)IDH1/2 has been developed as one biomarker for tumor diagnosis;4)IDH2 mutation plays a critical role in proliferation,apoptosis,invasion,migration,tumorgenesis,and senescence,indicating that targeting IDH mutant become a therapeutic strategy in cancers.Due to IDH oncogenic function in cancers,we are focusing on studying the relationship of protein structure,function and stability in IDH mutants,try to get valuable information for targeting IDH therapies.