The human ABCG2 is an important plasma membrane multidrug transporter, involved in
uric acid secretion, modulation of absorption of drugs, and in drug resistance of
cancer cells. Variants of the ABCG2 transporter, affecting cellular processing and
trafficking, have been shown to cause gout and increased drug toxicity. In this paper,
we overview the key cellular pathways involved in the processing and trafficking of
large membrane proteins, focusing on ABC transporters. We discuss the information
available for disease-causing polymorphic variants and selected mutations of ABCG2,
causing increased degradation and impaired travelling of the transporter to the plasma
membrane. In addition, we provide a detailed in silico analysis of an as yet unrecognized
loop region of the ABCG2 protein, in which a recently discovered mutation may actually
promote ABCG2 membrane expression. We suggest that post-translational modifications
in this unstructured loop at the cytoplasmic surface of the protein may have special
influence on ABCG2 processing and trafficking.
