GPI (Glucose-6-phosphate isomerase) belongs to the GPI family whose members are multifunctional phosphoglucose isomerase proteins. GPI is involved in energy pathways and it is an enzyme that catalyzes the conversion of glucose-6-phosphate into fructose 6-phosphate in the second step of glycolysis. The protein has different capacities inside and outside the cell. In the cytoplasm, the gene product is involved in glycolysis and gluconeogenesis, while outside the cell it functions as a neurotrophic factor for spinal and sensory neurons. Defects in GPI are the cause of nonspherocytic hemolytic anemia and a severe enzyme deficiency can be associated with hydrops fetalis, immediate neonatal death and neurological impairment.