Asialoglycoprotein Receptor (ASGPR)

Asialoglycoprotein Receptor (ASGPR), also known as the Ashwell-Morell receptor, is a C-type lectin highly and specifically expressed on the surface of hepatocytes. It was the first cell surface lectin discovered in mammals. ASGPR is composed of two subunits (H1 and H2) and contains calcium-dependent carbohydrate recognition domains (CRDs) that can recognize terminal D-galactose (Gal) or N-acetylgalactosamine (GalNAc) residues on desialylated glycoproteins.
ASGPR mediates the internalization of its ligands via clathrin-mediated endocytosis and remains recyclable after internalization, showing great potential for efficient delivery. It plays a critical role in the clearance of desialylated glycoproteins such as IgA, extracellular fibronectin, and hepatic lipoproteins, and is also involved in the hepatic entry of certain pathogens.
Due to its high expression in hepatocytes (approximately 500,000 receptors per cell) and minimal expression in other tissues, ASGPR serves as an ideal target for liver-specific drug delivery. ASGPR-targeted delivery strategies often utilize natural or synthetic sugar-based ligands (e.g., arabinogalactan, pullulan, or GalNAc-modified polymers) to construct ligand-drug conjugates or ligand-anchored nanocarriers for selective uptake by hepatocytes.
Dysregulated expression or impaired function of ASGPR is closely associated with various diseases, including viral hepatitis, hepatocellular carcinoma, autoimmune hepatitis, diabetes, and drug-induced liver injury. ASGPR is not only a valuable therapeutic target but also holds potential in liver function evaluation and clinical diagnostics^[1].