The ASGR2 protein (Asialoglycoprotein Receptor Subtype 2) is a type II transmembrane receptor primarily expressed on the surface of hepatocytes and belongs to the C-type lectin superfamily. It forms hetero-oligomeric complexes with ASGR1, mediating the endocytosis and lysosomal degradation of desialylated glycoproteins in the bloodstream by recognizing terminal galactose or N-acetylgalactosamine residues. This process plays a critical role in maintaining glycoprotein homeostasis and regulating cholesterol metabolism. ASGR2 exhibits liver-specific high expression, featuring a calcium-dependent carbohydrate-recognition domain (CRD) in its extracellular region. Recent studies have identified the ASGR signaling pathway's involvement in lipid metabolism disorders, liver fibrosis, and hepatocellular carcinoma progression. Targeted therapies (e.g., ASGR1/2 inhibitors) show potential for cholesterol-lowering treatments, possibly by modulating the PCSK9/LDLR pathway. Additionally, ASGR2 is utilized in designing liver-targeted drug delivery systems, leveraging its efficient internalization capacity to enhance liver-specific accumulation of therapeutic molecules.
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