Siglecs are vertebrate cell-surface lectins that recognize sialylated glycans and are involved in many physiological processes, such as glycoprotein turnover, cellular trafficking, and pathogen recognition. Most Siglecs are expressed on cells of the immune system. SIGLEC15 is a type-I transmembrane protein consisting of two immunoglobulin (Ig)-like domains, a transmembrane domain containing a lysine residue, and a short cytoplasmic tail. SIGLEC15 can interact with the activating adaptor molecules DAP12/10. Its activating signaling potential and unique preference for glycan recognition implies that SIGLEC15 may be involved in the immune surveillance of tumors and probably plays a conserved, regulatory role in the immune system of vertebrates.