Sialic acid-binding immunoglobulin-like lectin 12 (SIGLEC12)

Sialic acid-binding immunoglobulin-like lectin 12 (SIGLEC12) is a cell surface receptor belonging to the immunoglobulin superfamily, specifically the CD33-related subgroup of Siglecs. In humans, SIGLEC12 is unusual due to a fixed mutation that abolishes strong sialic acid binding, though its inhibitory intracellular signaling motifs (ITIM) remain functional. SIGLEC12 is expressed in certain immune and epithelial cells, particularly in some carcinomas such as prostate cancer, and may play a role in regulating cell adhesion and immune responses by recruiting phosphatases SHP-1/SHP-2 upon phosphorylation. Its expression and function are polymorphic in humans, with a significant percentage carrying an inactivating frameshift allele rendering the protein absent. SIGLEC12 has been considered a putative therapeutic target in cancer for antibody-drug conjugate approaches but is not currently the target of approved drugs. Its overall biological and pathological roles remain partially elucidated, with current evidence suggesting involvement in immune regulation and epithelial cancer progression.

Other names

Siglec-12Siglec-XIISIGLECL1SIGLEC-like 1sialic acid-binding Ig-like lectin 12Sialic acid-binding Ig-like lectin-like 1SLGS2VSiglec-L1

Experimental: Antibody-mediated targeting for selective cell death (e.g., antibody-toxin conjugates induce receptor-mediated internalization and cell death in cancer cells expressing SIGLEC12)