Molecular regulation of the hepatic bile acid uptake transporter and HBV entry receptor NTCP

Transporters expressed by hepatocytes and enterocytes play a critical role in maintaining the enterohepatic circulation of bile acids. The sodium taurocholate cotransporting polypeptide (NTCP), exclusively expressed at the basolateral side of hepatocytes, mediates the uptake of conjugated bile acids. In conditions where bile flow is impaired (cholestasis), pharmacological inhibition of NTCP-mediated bile acid influx is suggested to reduce hepatocellular damage due to bile acid overload. Furthermore, NTCP has been shown to play an important role in hepatitis B virus (HBV) and hepatitis Delta virus (HDV) infection by functioning as receptor for viral entry into hepatocytes. This review provides a summary of current molecular insight into the regulation of NTCP expression at the plasma membrane, hepatic bile acid transport, and NTCP-mediated viral infection. •Complementary mechanisms exist to downregulate bile acid uptake during cholestasis.•Pharmacological NTCP inhibition is hepatoprotective in cholestasis.•HBV/HDV entry requires NTCP and can be inhibited by a pre-S1 mimicking peptide.•Inhibition of NTCP could be beneficial in metabolic disorders.