C-type lectin domain family 5 member A (CLEC5A)

C-type lectin domain family 5 member A (CLEC5A) is a type II transmembrane protein belonging to the C-type lectin receptor family, expressed predominantly on myeloid cells such as neutrophils, monocytes, macrophages, osteoclasts, microglia, and dendritic cells. Structurally, CLEC5A features a lectin-like domain and requires the adaptor protein DAP12 for signal transduction through the Syk kinase pathway; this is due to its short cytoplasmic tail that lacks signaling motifs. CLEC5A is a critical macrophage receptor for several viruses (notably dengue, influenza, and Japanese encephalitis virus): viral binding triggers DAP12 phosphorylation and causes secretion of pro-inflammatory cytokines, amplifying the innate immune response and contributing to diseases such as dengue hemorrhagic fever and dengue shock syndrome. CLEC5A also positively regulates osteoclastogenesis and participates in virus-induced pathology and inflammatory diseases. CLEC5A is under active investigation as a therapeutic target by blocking its activity (e.g., monoclonal antibodies, Syk inhibitors) to attenuate inflammatory damage in viral infections.

Other names

C-type lectin domain containing 5ACLEC5ACLECSF5MDL1MDL-1C-type lectin superfamily member 5Myeloid DAP12-associating lectin 1

Blockade of ligand binding to CLEC5A inhibits downstream signaling and pro-inflammatory cytokine release; Syk pathway inhibition interrupts signal transduction after CLEC5A activation