Solute carrier family 10 member 1 (SLC10A1) (SLC10A1)

Solute carrier family 10 member 1 (SLC10A1), commonly known as the sodium taurocholate cotransporting polypeptide (NTCP), is a key transmembrane protein primarily expressed on the basolateral membrane of hepatocytes [8, 10]. Its primary physiological role is the sodium-dependent uptake of conjugated bile acids from the portal blood into the liver, which is essential for maintaining the enterohepatic circulation of bile salts and cholesterol homeostasis [8, 13]. Beyond its transport function, SLC10A1 has been identified as the critical cellular entry receptor for the hepatitis B virus (HBV) and hepatitis D virus (HDV) [1, 9, 18]. The virus utilizes the preS1 domain of its large surface protein to bind to NTCP, facilitating viral internalization [3, 4, 16]. This dual role makes SLC10A1 a significant therapeutic target, particularly for the treatment of chronic hepatitis D [4, 9]. The drug bulevirtide (Hepcludex) is a first-in-class entry inhibitor that binds to NTCP with high affinity, effectively blocking viral entry and reducing viral load [1, 4, 6]. While inhibiting NTCP can lead to elevated systemic bile acid levels (hypercholanemia), this is generally well-tolerated and serves as a pharmacodynamic biomarker for target engagement [4, 15, 19].

Other names

Sodium taurocholate cotransporting polypeptideNTCPNa+/taurocholate cotransporting polypeptideSodium/bile acid cotransporterNa+/bile acid cotransporterNa+/taurocholate transport proteinGGVVKCell growth-inhibiting gene 29 protein

Bulevirtide acts as a viral entry inhibitor by binding with high affinity to the NTCP receptor on the basolateral membrane of hepatocytes, thereby blocking the interaction between the HBV/HDV preS1 domain and the receptor [1, 3, 4]. This prevents the viruses from entering and infecting new liver cells [4, 5]. Additionally, drugs can inhibit the physiological function of NTCP as a sodium-dependent bile acid transporter, leading to elevated systemic bile acid levels [6, 9].