Leukocyte-Associated Immunoglobulin-Like Receptor 1 (LAIR1) is a single-pass type I membrane protein. LAIR1 expressed on the majority of peripheral mononuclear cells, including natural killer (NK) cells, T-cells, B-cells, monocytes, and dendritic cells, highly in naive T-cells and B-cells. As an inhibitory receptor, LAIR1 plays a constitutive negative regulatory role on cytolytic function of natural killer (NK) cells, B-cells and T-cells. Activation by Tyr phosphorylation results in recruitment and activation of the phosphatases PTPN6 and PTPN11. It also reduces the increase of intracellular calcium evoked by B-cell receptor ligation. LAIR1 plays inhibitory role independently of SH2-containing phosphatases and modulates cytokine production in CD4+ T-cells. It down-regulates IL2 and IFNG production while inducing secretion of transforming growth factor beta, also down-regulates IgG and IgE production in B-cells as well as IL8, IL10 and TNF secretion. LAIR1 inhibits the differentiation of peripheral blood precursors towards dendritic cells. It also restrains proliferation and induces apoptosis in myeloid leukemia cell lines as well as prevents nuclear translocation of NF-kappa-B p65 subunit/RELA and phosphorylation of I-kappa-B alpha/CHUK in these cells.