Catalyzes the NADP(+)-dependent oxidative decarboxylation of isocitrate (D-threo-isocitrate) to 2-ketoglutarate (2-oxoglutarate), which is required by other enzymes such as the phytanoyl-CoA dioxygenase (PubMed:10521434, PubMed:19935646). Plays a critical role in the generation of NADPH, an important cofactor in many biosynthesis pathways (PubMed:10521434). May act as a corneal epithelial crystallin and may be involved in maintaining corneal epithelial transparency (By similarity). D-threo-isocitrate + NADP(+) = 2-oxoglutarate + CO2 + NADPH Binds 1 Mg(2+) or Mn(2+) ion per subunit. Homodimer. Acetylation at Lys-374 dramatically reduces catalytic activity. The gene represented in this entry is involved in disease pathogenesis. Mutations affecting Arg-132 are tissue-specific, and suggest that this residue plays a unique role in the development of high-grade gliomas. Mutations of Arg-132 to Cys, His, Leu or Ser abolish magnesium binding and abolish the conversion of isocitrate to alpha-ketoglutarate. Instead, alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate. Elevated levels of R(-)-2-hydroxyglutarate are correlated with an elevated risk of malignant brain tumors. Genetic variations are associated with cartilaginous tumors such as enchondroma or chondrosarcoma. Mutations of Arg-132 to Cys, Gly or His abolish the conversion of isocitrate to alpha-ketoglutarate. Instead, alpha-ketoglutarate is converted to R(-)-2-hydroxyglutarate. Belongs to the isocitrate and isopropylmalate dehydrogenases family. Isocitrate dehydrogenase entry