ATP-binding cassette sub-family G member 8 (ABCG8) (ABCG8)

ATP-binding cassette sub-family G member 8 (ABCG8) is a half-transporter that forms an obligate heterodimer with ABCG5 to create a functional sterol efflux pump known as sterolin (UniProt: Q9H221, MedlinePlus). Primarily expressed on the apical membranes of enterocytes and the canalicular membranes of hepatocytes, this complex is essential for maintaining whole-body sterol homeostasis by promoting the excretion of cholesterol and plant sterols into the bile and intestinal lumen (NCBI Gene, PMC: PMC2724524). Loss-of-function mutations in ABCG8 cause sitosterolemia, a rare metabolic disorder characterized by the systemic accumulation of phytosterols, leading to xanthomas and accelerated cardiovascular disease (PMC: PMC7451435). Conversely, gain-of-function variants or overactivity of the transporter are major risk factors for the development of cholesterol gallstones due to the supersaturation of bile with cholesterol (PMC: PMC2724524). ABCG8 is a significant target for lipid-modulating therapies; its expression is induced by Liver X Receptor (LXR) agonists to enhance cholesterol clearance, and its deficiency is clinically managed with ezetimibe to restrict sterol absorption (PMC: PMC7451435, PMC: PMC6822395). Emerging evidence also links ABCG8 expression to radiotherapy resistance and progression in certain cancers, such as triple-negative breast cancer (Int J Mol Med, 2025).

Other names

Sterolin-2STSLGBD4ATP-binding cassette, sub-family G (WHITE), member 8

ABCG8 functions as an obligate heterodimer with ABCG5 to form a sterol efflux pump. Therapeutic strategies involve the upregulation of this complex via Liver X Receptor (LXR) agonists to increase biliary cholesterol excretion and reduce intestinal absorption (PMC: PMC2724524). In cases of ABCG8 deficiency (sitosterolemia), NPC1L1 inhibitors like ezetimibe are used to block the primary entry route of sterols, compensating for the lack of efflux capacity (PMC: PMC7451435). Additionally, phytosterols act as competitive substrates for the transporter (PMC: PMC2724524).