Glucose-6-phosphate isomerase (also known as phosphoglucose isomerase (PGI)) is an enzyme that catalyzes the reversible aldose-ketose isomerization of glucose 6-phosphate (G6P) to fructose 6-phosphate (F6P). The reaction has direct roles in glycolysis and gluconeogenesis and, indirectly, other branches of carbohydrate metabolism such as the pentose phosphate pathway. PGI belongs to the aldose-ketose isomerase family of enzymes, all of which transfer a hydrogen atom between C1 and C2 of their respective substrates. PGIs use sugar substrates that exist in solution overwhelmingly in the hemiacetal or hemiketal ring form. PGIs also have a number of ‘moonlighting’ functions: it acts as an autocrine motility factor (AMF) and neuroleukin agent (NLK), a serine proteinase inhibitor and a differentiation and maturation mediator (DMM). It was found that GPI plays an essential role in the development of arthritis in mammals and may play roles in both cancer and autoimmunity.