Hepatic uptake and biliary excretion of bile salts and non-bile salt organi
c anions (e. g., bilirubin) is mediated by specific transport proteins loca
ted at the basolateral and canalicular membranes of hepatocytes. Several he
patobiliary transport systems have been identified and cloned over the past
years. This development has facilitated molecular biological and genetic a
nalyses of these transporters in experimental cholestasis and human cholest
atic liver diseases. Evidence now exists that decreased or even absent expr
ession of hepatobiliary transport systems may explain impaired transport fu
nction resulting in hyperbilirubinemia and cholestasis. This review summari
zes the molecular defects in hepatocellular membrane transporters associate
d with hereditary and acquired forms of cholestatic liver diseases. The inc
reasing information on the molecular regulation of hepatobiliary transport
systems should bring new insights into the pathophysiology and treatment of
human cholestatic liver diseases.