CLEC4E (Mincle) is a calcium-dependent C-type lectin pattern recognition receptor that recognizes both pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs) 12. Its primary ligand is mycobacterial trehalose 6,6'-dimycolate (TDM), a potent immunomodulatory cell wall glycolipid that triggers SYK/CARD9/NF-κB signaling through FCER1G-mediated ITAM phosphorylation, driving T-helper 1 and T-helper 17 cell differentiation 23. CLEC4E also recognizes fungal α-mannose residues and senses DAMPs from damaged cells, promoting macrophage activation and inflammatory responses 1. Functionally, CLEC4E mediates trained immunity in bone marrow progenitors following microbiota translocation 4 and is differentially expressed in acute lung injury models 5. In tuberculosis, CLEC4E polymorphisms (rs10841845, rs10841847) confer protective genetic associations in Chinese populations 6, though one study found no conclusive associations 7. Pathologically, high CLEC4E expression in tumor-associated macrophages correlates with poor melanoma prognosis; CLEC4E knockout suppresses tumor growth by reducing TAM proliferation and enhancing T-cell cytotoxicity 8. CLEC4E is elevated in systemic lupus erythematosus and ischemic stroke, serving as a diagnostic and prognostic biomarker 910. The miR-22-5p/CLEC4E axis is implicated in nonalcoholic fatty liver disease pathogenesis 11.