Dear Editor,

Bile salts are the major organic solutes in bile, the secretion of which is crucial to the viability of hepatocytes as its intracellular accumulation in the liver will ultimately results in cell death.1 Human ABCB11, also known as bile salts export pump (BSEP), is the major exporter for the specific secretion of bile salts. Correspondingly, defects of ABCB11 function, due to either mutations or side effects of medicines, lead to inherited or acquired diseases, respectively, such as progressive familial intrahepatic cholestasis type 2 (PFIC2), benign recurrent intrahepatic cholestasis type 2 (BRIC2), and drug-induced cholestasis (DIC). The severe cholestasis PFIC2 is usually found in newborn patients, which could rapidly progress to cirrhosis, with the possibility of hepatocellular carcinoma and cholangiocarcinoma occurring under one-year age.5 As deposited in the Human Gene Mutation Database (http://www.hgmd.cf.ac.uk/), more than 300 different clinical mutations in ABCB11 gene, including missense, nonsense, aberrant splicing, deletions and insertions, have been identified from cholestatic patients. Despite ABCB11 shares a sequence identity of ~48% with two structure-known transporters ABCB1 and ABCB4, which are ~71% sequence-identical to each other, the three transporters differ significantly in substrate specificity. ABCB1 and ABCB4 could transport various organic cations and phosphatidylcholine, respectively, whereas ABCB11 selectively transports bile salts.6 However, the molecular mechanisms of transport and substrate specificity remain unclear, even for the structure-known ABCB1 and ABCB4.

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