Asialoglycoprotein receptor 1 (ASGR1) (ASGR1)

The Asialoglycoprotein receptor 1 (ASGR1) is the major subunit of the asialoglycoprotein receptor (ASGPR), a hetero-oligomeric C-type lectin predominantly expressed on the sinusoidal surface of hepatocytes. Its primary biological function is the homeostatic regulation of serum glycoprotein levels through the recognition and clearance of desialylated (asialo) glycoproteins from the systemic circulation via receptor-mediated endocytosis. ASGR1 specifically binds terminal galactose or N-acetylgalactosamine (GalNAc) residues, facilitating their internalization and subsequent lysosomal degradation. This high-capacity, liver-specific uptake mechanism is extensively exploited in modern biotechnology for the targeted delivery of N-acetylgalactosamine (GalNAc)-conjugated therapeutics, including several approved siRNA and antisense oligonucleotide drugs for metabolic and genetic disorders. Furthermore, ASGR1 has emerged as a target of interest in cardiovascular medicine; human genetic studies have demonstrated that loss-of-function variants in the ASGR1 gene are associated with significantly lower levels of LDL cholesterol and a reduced risk of coronary artery disease. Beyond its role in metabolism, the receptor can be exploited by certain pathogens and is a key factor in the clearance of aged or damaged cells and proteins.

Other names

Asialoglycoprotein receptorASGPRAshwell-Morell receptorHepatic lectinASGRHL-1Asialoglycan receptor

Receptor-mediated endocytosis for liver-specific delivery of GalNAc-conjugated payloads