Hydrolyzes glucose-6-phosphate to glucose in the endoplasmic reticulum. May form with the glucose-6-phosphate transporter (SLC37A4/G6PT) a ubiquitously expressed complex responsible for glucose production through glycogenolysis and gluconeogenesis. Probably required for normal neutrophil function. D-glucose 6-phosphate + H2O = D-glucose + phosphate Inhibited by vanadate. Optimum pH is 6.5. Optimum temperature is 37 degrees Celsius. Carbohydrate biosynthesis; gluconeogenesis. Widely expressed. Highly expressed in heart and testis and to a lower extent in spleen, stomach, small intestine, skeletal muscle and uterus. Expressed in muscle, brain, thymus, lung, kidney, spleen and pancreas (at protein level). In the brain, expressed in astrocytes (at protein level) (PubMed:15661744). Mice display reduced glucose-6-phosphate hydrolytic activity in the brain. No phenotypic difference was noted at birth but 4 months old female mice display growth retardation. Mutant mice exhibit a decreased plasma cholesterol concentration and an increased plasma glucagon concentration but no difference in blood glucose concentration (PubMed:17023421). Mice display neutropenia and neutrophil dysfunctions. Belongs to the glucose-6-phosphatase family.