yet been clarified. But it is suggested that the ABCG5/ABCG8 heterodimer shuttles cholesterol from the inner leaflet of the canalicular membrane through a chamber formed by the two half-transporters. Following ATP binding and hydrolysis, the complex undergoes a conformational change, flipping a cholesterol molecule into the outer membrane leaflet in a configuration that favors its release into the canalicular space. Based on the clinical defects in sitosterolemia, ABCG5/ABCG8 are expressed in the liver and/or the intestine. 5 These genes respond to environmental dietary sterols, although whether they are also increased by high phytosterols has yet to be determined. It is worth to mention that other gene products play a role in dietary-cholesterol transport (such as ABCA1). Disorders involving ABCG5 and ABCG8 genes Mutations in both alleles of either ABCG5 or ABCG8 in the human results in sitosterolemia. Sitosterolemia (also known as phytosterolemia) is a rare autosomal recessively inherited lipid metabolic disorder characterized by the presence of tendon xanthomas, premature coronary artery disease and atherosclerotic disease, hemolytic episodes, arthralgias and arthritis. The hallmark of sitosterolemia is diagnostically elevated levels of plant sterols in the plasma. References Lee M, Lu K, Patel S B. Genetic basis of sitosterolemia. Curr. Opin. Lipidol., 2001; 12(2): 141–149. Patel S B, Salen G, Hidaka H, Kwiterovich P O, Stalenhoef A F, Miettinen T A, Grundy S M, Lee M H, Rubenstein J S, Polymeropoulos M H, Brownstein M J. Mapping a gene involved in regulating dietary cholesterol absorption. The sitosterolemia locus is found at chromosome 2p21. J. Clin. Invest., 1998;102: 1041–1044. Lee M H, Gordon D, Ott J, Lu K, Ose L, Miettinen T, Gylling H, Stalenhoef A F, Pandya A, Hidaka H, B Jr. Brewer, Kojima H, Sakuma N, Pegoraro R, Salen G, Patel S B. Fine mapping of a gene responsible for regulating dietary cholesterol absorption: founder effects underlie cases of phytosterolaemia in multiple communities. Eur. J. Hum. Genet. 2001;9: 375–384. Lee M-H, Lu K, Hazard S, Yu H, Shulenin S, Hidaka H, Kojima H, Allikmets R, Sakuma N, Pegoraro R, Srivastava AK, Salen G, Dean M, Patel SB Identification of a gene, ABCG5, important in the regulation of dietary cholesterol absorption. Nat Genet, 2001;27:79–83. Lu K, Lee M-H, Hazard S,Brooks-Wilson A, Hidaka H, Kojima H, Ose L, Stalenhoef A F H,Mietinnen T,Bjorkhem I,Bruckert E, Pandya A, Brewer H B Jr., Salen G,Dean M,Srivastava A, Patel S B. Two genes that map to the