The leukocyte-associated Ig-like receptor-1 (CD305) is an ITIM-containing inhibitory immune receptor, belonging to the Ig superfamily. LAIR-2 is encoded by a gene located in the vicinity of the LAIR-1 gene in the leukocyte receptor complex on human chromosome 19q13.4. The predicted LAIR-2 protein has a single Ig-like domain sharing 84% sequence homology with hLAIR-1, and the molecule lacks a transmembrane and cytoplasmic region suggesting it is a secreted protein. In contrast to hLAIR-1, LAIR-2 has no orthologs in mice or rats. The membrane ligand for LAIR-1 and LAIR-2 was expressed extensively and ligand recognition was of cross-species. LAIR-2 blocked the interaction of LAIR-1 with its ligand but LAIR-1 didn't block the interaction of LAIR-2 with its ligand. LAIR-2 had a higher affinity for collagen than did LAIR-1. LAIR-2 is a more potent antagonist of LAIR-1 function in vivo, while both sLAIR-1 and LAIR-2 are potential biomarkers. Recently shown that recombinant LAIR-2–Fc is able to interfere with collagen-induced platelet aggregation and that it efficiently inhibits the binding of collagen to glycoprotein VI and von Willebrand factor.