Isocitrate dehydrogenase [NADP], mitochondrial

IDH2 (isocitrate dehydrogenase [NADP], mitochondrial) is a 452-amino-acid enzyme that catalyzes a key step in intermediary metabolism and energy production (UniProt: P48735). The protein may associate with the pyruvate dehydrogenase complex and functions in mitochondrial redox and biosynthetic pathways.

IDH2 is implicated in neurometabolic disorders, notably D-2-hydroxyglutaric aciduria 2 (D2HGA2), a developmental encephalopathy characterized by early-onset epilepsy, hypotonia, and developmental delay (UniProt: P48735). Mutations in IDH2 can produce aberrant D-2-hydroxyglutaric acid accumulation. The enzyme is also associated with glioma pathogenesis (UniProt: P48735).

In Alzheimer's disease, IDH2 is significantly upregulated in post-mortem AD brain tissue compared to age-matched controls (mean log2 fold-change: +0.31; Chaparral AD proteomics). This elevation in human AD brain suggests altered mitochondrial metabolism and energy homeostasis may contribute to disease pathology, consistent with the emerging evidence linking bioenergetic dysfunction to neurodegeneration.