Glucose-6-phosphate isomerase

Glucose-6-phosphate isomerase (GPI) is a metabolic enzyme that catalyzes the interconversion of glucose-6-phosphate and fructose-6-phosphate, central reactions in glycolysis and gluconeogenesis within the cytoplasm (UniProt: P06744). Beyond its canonical enzymatic role, GPI also functions as a secreted cytokine, acting as autocrine motility factor to enhance endothelial cell migration and as neuroleukin to support spinal and sensory neuron survival (UniProt: P06744). Pathogenic variants cause congenital non-spherocytic hemolytic anemia type 4 (UniProt: P06744).

GPI shows ambiguous regulation across subcellular fractions in Alzheimer's disease brain tissue compared to age-matched controls, with a mean log2 fold-change of 0.3993 across three fractions measured by quantitative proteomics (Chaparral AD proteomics). This modest, inconsistent change suggests variable abundance depending on subcellular compartment or cellular context in AD pathology, warranting further investigation into whether altered GPI distribution or expression contributes to AD-related metabolic dysfunction.