C-type lectin domain family 4 member E (CLEC4E)

C-type lectin domain family 4 member E (CLEC4E), commonly known as Mincle, is a type II transmembrane protein of the C-type lectin receptor family, functioning as a pattern recognition receptor in the innate immune system[1][2][3][4][5]. CLEC4E is primarily expressed in myeloid cells (macrophages, dendritic cells, monocytes), where it recognizes glycolipid patterns from pathogens (such as the mycobacterial cord factor trehalose-6,6′-dimycolate) and endogenous danger signals released during tissue damage[2][1][3][4][5]. Upon binding its ligands, CLEC4E associates with the FcRγ chain, leading to phosphorylation of ITAM motifs and downstream activation of Syk kinase, CARD9 signaling, and NF-κB. This results in the induction and propagation of inflammatory cytokine production, shaping T-cell responses and driving both pathogen defense and tissue repair, but also contributing to sterile inflammation and pathology in diseases such as myocardial infarction[5][3][4][2]. CLEC4E is being studied as both a biomarker and a novel therapeutic target in infectious, inflammatory, and cardiovascular diseases[5][2][3].

Other names

CLEC4EMincleCLECSF9Macrophage-inducible C-type lectinC-type lectin superfamily member 9UNQ218/PRO244C-type lectin domain family 4 member EC-type (calcium-dependent, carbohydrate-recognition domain) lectin, superfamily member 9

Agonists (e.g., cord factor/TDM analogs) promote immune activation, enhance inflammation, or adjuvanticity. Inhibitors (not yet established clinically) would reduce inflammation by blocking DAMP/PAMP recognition and downstream cytokine production. Both modes regulate signal transduction via Fc receptor γ-chain (FcRγ), Syk kinase, and NF-κB activation.