摘要Glycogen storage disease type Ⅰa(GSD-Ⅰa)is an autosomal recessive metabolic disorder caused by a deficiency in glucose-6-phosphatase-α(G6Pase-α or G6PC)that is expressed primarily in the liver,kidney,and intestine.G6Pase-α catalyzes the hydrolysis of glucose-6-phosphate(G6P)to glucose and phosphate in the terminal step of gluconeogenesis and glycogenolysis,and is a key enzyme for endog-enous glucose production.The active site of G6Pase-α is inside the endoplasmic reticulum(ER)lumen.For catalysis,the substrate G6P must be translocated from the cytoplasm into the ER lumen by a G6P transporter(G6PT).The functional coupling of G6Pase-α and G6PT maintains interprandial glucose ho-meostasis.Dietary therapies for GSD-Ⅰa are available,but cannot prevent the long-term complication of hepatocellular adenoma that may undergo malignant transformation to hepatocellular carcinoma.Ani-mal models of GSD-Ⅰa are now available and are being exploited to both delineate the disease more precisely and develop new treatment approaches,including gene therapy.