Sialic acid-binding immunoglobulin-like lectin 16 (SIGLEC16)

Sialic acid-binding immunoglobulin-like lectin 16 (SIGLEC16) is a transmembrane receptor of the Siglec family, primarily expressed on human macrophages and microglia. SIGLEC16 binds sialylated glycans, especially polysialic acid, via its immunoglobulin-like domains. Its signal transduction requires association with the DAP12 adaptor protein, which contains an immunoreceptor tyrosine-based activation motif (ITAM), conferring *activating* proinflammatory functions in contrast to its paralog, SIGLEC11, which is inhibitory. SIGLEC16 modulates immune responses in the tumor microenvironment by promoting M1-like macrophage polarization, elevating proinflammatory cytokine secretion (e.g., TNF, IL-6) and enhancing anti-tumor immune responses in glioblastoma; functional SIGLEC16 and polySia co-expression is associated with improved patient survival. SIGLEC16 has unique population genetics, with a large fraction of humans expressing only a non-functional pseudogene (SIGLEC16P) due to a four-nucleotide deletion, while about 38–50% retain the ability to express the functional protein. SIGLEC16 does not have a rodent ortholog, limiting preclinical model studies. No currently approved drugs target this molecule directly.

Other names

Sialic acid-binding Ig-like lectin 16SIGLEC16SIGLECP16Siglec-16Siglec-P16sialic acid-binding Ig like lectin 16sialic acid binding Ig-like lectin 16sialic acid binding Ig-like lectinsialic acid-binding Ig-like lectin 16sialic acid binding Ig-like lectin, pseudogene 16sialic acid-binding immunoglobulin-like lectin 16siglec-16

Not applicable (no known drugs), but functionally mediates activating immune signaling by binding sialylated glycans, transducing signals via DAP12 ITAM