Sialic acid-binding immunoglobulin-like lectin (Siglec) receptor family (Siglec)

Siglecs are a family of cell surface receptor proteins that specifically bind to sialic acid-containing glycans. Characterized as immunoglobulin-like lectins, Siglecs are predominantly expressed by immune cells and mediate pivotal roles in regulating immune cell activation, tolerance, and phagocytosis. A central function is the discrimination of “self” (host) vs. “non-self” (pathogen or altered) based on the sialylation patterns of glycoproteins and glycolipids. Their signaling, mostly through inhibitory cytoplasmic ITIM motifs, dampens immune activation, but some Siglecs also convey activating signals via association with ITAM-containing adaptors. Siglecs have direct relevance in disease pathogenesis (notably cancer, neurodegeneration, allergy, and infection), making them attractive targets for monoclonal antibodies, antibody-drug conjugates, CAR-T therapies, and checkpoint inhibitor strategies. Their complex biology also presents therapeutic challenges for safety and selectivity.

Other names

Sialic acid-binding immunoglobulin-type lectinsSialic acid-binding Ig-like lectinsCD33-related Siglecs (for a major subfamily)

Antibody-dependent cell-mediated cytotoxicity Cargo delivery via receptor-mediated endocytosis (e.g., antibody-drug conjugates) Immune checkpoint modulation (inhibition of activation via ITIMs or stimulation via ITAMs in some subtypes) Blocking sialic acid–Siglec interactions to enhance anti-tumor immunity (checkpoint blockade) Cell depletion (via direct targeting and cytotoxic payloads)