Along with many other mammalian
ATP-binding cassette (
ABC) transporters, members of the ABCG group are involved in the regulated transport of hydrophobic compounds across cellular membranes. In humans, five ABCG family members have been identified, encoding
proteins ranging from 638 to 678
amino acids in length. All five have been the subject of intensive investigation to better understand their physiological roles, expression patterns, interactions with substrates and inhibitors, and regulation at both the transcript and
protein level. The principal substrates for at least four of the
ABCG proteins are endogenous and dietary
lipids, with ABCG1 implicated in particular in the export of
cholesterol, and ABCG5 and G8 forming a functional heterodimer responsible for
plant sterol elimination from the body. ABCG2 has a much broader substrate specificity and its ability to transport numerous diverse
pharmaceuticals has implications for the absorption, distribution, metabolism, excretion and toxicity (ADMETOx) profile of these compounds. ABCG2 is one of at least three so-called multidrug resistant
ABC transporters expressed in humans, and its activity is associated with decreased efficacy of anti-
cancer agents in several
carcinomas. In addition to its role in
cancer, ABCG2 also plays a role in the normal physiological transport of
urate and
haem, the implications of which are described. We summarize here data on all five human
ABCG transporters and provide a current perspective on their roles in human health and disease.