CLEC4F (C-type lectin domain family 4 member F) is a galactose-binding C-type lectin receptor with critical roles in immune homeostasis and pathogen recognition. The protein functions as a pattern recognition receptor expressed on the surface of Kupffer cells (liver-resident macrophages) and contains a carbohydrate-recognition domain that specifically binds galactose and galactose-containing glycans 1. Structurally, CLEC4F forms unique trimeric complexes with polyglutamine interactions in its neck region, positioning glycan-binding sites approximately 45 Å apart—a configuration distinct from other C-type lectins 2. CLEC4F serves as a marker distinguishing resting Kupffer cells from infiltrating monocyte-derived macrophages, with expression downregulated during macrophage activation 3. The receptor mediates immune responses to parasitic glycostructures; LL mucin carbohydrates from Echinococcus parasites specifically interact with CLEC4F on Kupffer cells 4. In hepatocellular carcinoma, CLEC4F+ Kupffer cells are targeted in mouse models to study tumor-associated macrophage biology and their immunosuppressive effects on CD8+ T cells 56. Notably, functional CLEC4F is absent in humans due to splice site and missense mutations in the gene, though functional orthologs exist in other primates and species, suggesting CLEC4F evolved distinct immunological functions across species 1. A genome-wide association study linked CLEC4F to microbiome composition, indicating roles in host-microbe interactions 7.