ASGR2 encodes the minor subunit of the asialoglycoprotein receptor (ASGR), a hepatocyte-specific transmembrane lectin that mediates endocytosis of plasma glycoproteins with exposed terminal galactose or N-acetylgalactosamine residues 1. The receptor binds ligands at the cell surface, internalizes the complex, and returns to the membrane after cargo dissociation in sorting organelles. ASGR2 plays clinically significant roles beyond its canonical hepatic clearance function. In hemophilia A, ASGR2 genetic variants substantially modulate Factor VIII pharmacokinetics, with 5' untranslated region polymorphisms explaining up to 22% of parameter variability independent of ABO blood group 2. Similarly, ASGR2 variants interact with ABO genotype to influence Factor VIII levels in severe aortic stenosis 3. In gastric cancer, ASGR2 expression associates with poor prognosis: high expression predicts lymph node metastasis, venous invasion, and significantly reduced 5-year survival (55.5% vs 72.6%, p=0.009), serving as an independent poor prognostic factor 4 5. ASGR2 knockdown decreases cancer cell adhesion, migration, and invasive capacity, while suppressing hepatic metastasis formation 5. Additionally, ASGR2 was identified as a monocyte-associated biomarker for tuberculosis diagnosis and immunotherapy 6, and as a genetic risk factor associated with Alzheimer's disease and neuropsychiatric conditions 7.