Defective ABCG8 causes GBD4 and sitosterolemia

ATP-binding cassette sub-family G member 8 (ABCG8 aka sterolin-2), is a "half transporter", that forms a complex with another half transporter ABCG5 in the endoplasmic reticulum. This complex translocates to the plasma membrane to mediate the ATP-dependent intestinal absorption and facilitation of biliary secretion of cholesterol and phytosterols (eg sitosterol). Defects in either of these half transporters result in loss of enterocyte discrimination between cholesterol and sitosterol causing sterol accumulation and predisposition for atherosclerosis. Defects in ABCG8 are the cause of gallbladder disease 4 (GBD4; MIM:611465), one of the major digestive diseases. Gallstones are composed of cholesterol (cholelithiasis) and are the common manifestations of GBD in western countries. Defects in ABCG8 also cause sitosterolemia (MIM:210250), characterised by unrestricted intestinal absorption of both cholesterol and plant-derived sterols causing hypercholesterolemia and premature coronary atherosclerosis. Patients with sitosterolemia absorb between 15 and 60% of ingested sitosterol, and they excrete only a fraction into the bile.

Summary from Reactome (R-HSA-5679090), read 2026-09-23.