ABCG5G8

ABCG5 and ABCG8 are two closely related proteins encoded by the *ABCG5* and *ABCG8* genes, respectively, located on chromosome 2p21 in humans. These proteins belong to the ATP-binding cassette (ABC) transporter superfamily, specifically the G subfamily, and are primarily expressed in the intestine and liver. Their primary function is to regulate the absorption and excretion of sterols, including cholesterol and plant sterols (such as β-sitosterol), playing a critical role in lipid metabolism.

The ABCG5 and ABCG8 proteins form a heterodimer, meaning they function as a complex where both proteins are necessary for proper activity. This complex acts as an efflux transporter, moving sterols across cell membranes against their concentration gradient, a process that requires energy derived from ATP hydrolysis. In the intestine, ABCG5G8 limits the absorption of dietary plant sterols, thereby preventing excessive accumulation in the body. In the liver, it promotes the excretion of excess sterols into bile, helping maintain sterol homeostasis.

Mutations in either *ABCG5* or *ABCG8* can lead to sterol malabsorption syndromes, such as phytosterolemia, where elevated levels of plant sterols accumulate in tissues like the spleen, lymph nodes, and tendons. This condition is often associated with premature atherosclerosis and other complications. Genetic testing and dietary modifications, such as reducing plant sterol intake, are common approaches to managing these disorders.

Research on ABCG5G8 has also explored its potential role in cancer biology, as altered sterol metabolism may influence tumor growth and drug resistance. Additionally, the transporter has been investigated as a target for pharmaceutical interventions aimed at modulating cholesterol levels or improving the efficacy of certain medications. Further studies continue to elucidate its broader physiological and pathological significance.