CLEC4G (C-type lectin domain family 4 member G) is a glycan-binding pattern recognition receptor expressed on liver sinusoidal endothelial cells and neurons that functions as a viral entry receptor. It serves as a functional receptor for Lassa virus and Lymphocytic choriomeningitis virus glycoproteins 12. CLEC4G also acts as an ACE2-independent alternative receptor for SARS-CoV-2, binding to conserved N-glycan sites on the viral spike protein and mediating viral entry in a manner independent of ACE2 345. At the molecular level, CLEC4G recognizes carbohydrate structures on pathogenic glycoproteins, with its lectin-spike interactions occurring at sites within the RBD-ACE2 interface 3. Beyond viral pathogenesis, CLEC4G expression is significantly reduced in Alzheimer's disease brains, particularly in neurons, and associates with regulatory networks involving amyloid-β processing genes like BACE1 6. In endometrial cancer risk assessment, elevated circulating CLEC4G showed positive association 7. Additionally, CLEC4G is upregulated in chr19 rhinosinusitis with nasal polyps, potentially contributing to altered viral defense mechanisms 8. These findings suggest CLEC4G plays multifaceted roles in viral pathogenesis and neurodegenerative disease pathology.