GPI (glucose-6-phosphate isomerase) is a bifunctional enzyme with distinct intracellular and extracellular roles. Intracellularly, GPI catalyzes the reversible conversion of glucose-6-phosphate to fructose-6-phosphate, the second committed step of glycolysis and a key reaction in gluconeogenesis 1. The enzyme also exhibits C2-epimerase and anomerase activities on various hexose phosphates. Beyond its metabolic function, GPI operates as a secreted cytokine with multiple immunological and angiogenic properties. It functions as autocrine motility factor (AMF), enhancing endothelial cell motility and angiogenesis 2. GPI also acts as neuroleukin, a neurotrophic factor supporting spinal and sensory neuron survival 34. When released by lectin-stimulated T cells, GPI induces immunoglobulin secretion, contributing to humoral immune responses 34. GPI deficiency causes congenital non-spherocytic hemolytic anemia type 4, highlighting the critical importance of glycolytic flux for erythrocyte survival. The dual functionality of GPI—combining essential metabolic activity with cytokine-like immunomodulatory properties—represents a unique example of a housekeeping enzyme serving systemic regulatory roles.