ABCG8 encodes a subunit of an obligate heterodimer with ABCG5 that mediates ATP-dependent sterol transport across cell membranes 1. This transporter is essential for regulating whole-body sterol homeostasis by limiting intestinal cholesterol absorption and facilitating biliary cholesterol secretion into bile 2. The ABCG5/ABCG8 heterodimer functions as an efflux pump located on apical membranes of enterocytes and hepatocytes, eliminating sterols via the biliary tree and intestinal tract while preventing xenosterol accumulation 3. Loss-of-function mutations in ABCG8 cause sitosterolemia, an autosomal recessive disorder characterized by phytosterol and cholesterol accumulation in blood and tissues, leading to xanthomas, hemolytic anemia, and premature atherosclerosis 45. Common ABCG8 variants account for approximately 25% of genetic risk for gallstone disease 6. Additionally, even heterozygous carriers of ABCG8 variants show altered lipid profiles and increased cardiovascular risk 7. Therapeutic approaches include dietary sterol restriction and ezetimibe, a sterol absorption inhibitor that effectively reduces circulating lipid levels in affected patients 5. The transporter's role in sterol elimination is crucial for atherosclerosis prevention and metabolic disease management.