Glucose-6-phosphatase (G6Pase), is a multicomponent enzyme system that hydrolyzes glucose-6-phosphate in the final step of gluconeogenesis and gluconeolysis. G6Pase localizes to the endoplasmic reticulum, and while liver, kidney, and intestine are the only tissues that express the first identified isoform, G6Pase-alpha, a second form, designated G6Pase-∫, contributes to blood glucose homeostasis in a wider range of tissues. Islet-specific G-6-Pase catalytic subunit-related protein (IGRP), a homolog of the catalytic subunit of G6Pase, may play a role in the regulation of islet metabolism and in insulin secretion induced by metabolites. The exact catalytic acivity of IGRP is not defined. Identification of inhibitors of IGRP have potential therapeutic benefits for treatment of type 2 diabetes resulting from insulin secretion defects. Structurally, IGRP has been shown to be a glycoprotein held in the endoplasmic reticulum by nine transmembrane domains, which are then degraded in cells through the proteasome pathway generating MHC class I presented peptides.