The ABCG2 protein has a key role in the transport of a wide range of structurally
dissimilar endo- and xenobiotics in the human body, especially in the tissue barriers
and the metabolizing or secreting organs. The human ABCG2 gene harbors a high number
of polymorphisms and mutations, which may significantly modulate its expression and
function. Recent high-resolution structural data, complemented with molecular dynamic
simulations, may significantly help to understand intramolecular movements and substrate
handling, as well as the effects of mutations on the membrane transporter function
of ABCG2. As reviewed here, structural alterations may result not only in direct alterations
in drug binding and transporter activity, but also in improper folding or problems
in the carefully regulated process of trafficking, including vesicular transport,
endocytosis, recycling, and degradation. Here, we also review the clinical importance
of altered ABCG2 expression and function in general drug metabolism, cancer multidrug
resistance, and impaired uric acid excretion, leading to gout.
