Human Leukocyte Immunoglobulin-like Receptor Subfamily B Member 5 (LILRB5/CD85c/LIR-8) belongs to a family of transmembrane glycoproteins that negatively regulate immune cell activation. Mature human LIR-8 consists of a 435 amino acid (aa) extracellular domain with four Iglike domains, a 21 aa transmembrane segment, and a 111 aa cytoplasmic domain with two immunoreceptor tyrosine-based inhibitory motifs (ITIM). Alternative splicing of human LIR-8 generates an isoform that lacks the second Ig-like domain. LIR-8 is expressed on NK cells and in the tryptic granules of mast cells. Following cell activation and degranulation, it is present on the mast cell surface. Activated mast cells may also release soluble forms of LIR-8.