LMIR3, also known as CD300f, CD300LF, IREM-1, CLM-1, IgSF13, DIgR1, and MAIR-V, is a 50‑60 kDa glycoprotein member of the immunoglobulin superfamily. Alternate splicing generates additional isoforms that carry substituted C-terminal tails of varying lengths and sequences following the ECD or transmembrane segment. LMIR3 is expressed on the surface of dendritic cells, monocytes, granulocytes, and mast cells as well as on acute myeloid leukemia (AML) blasts. Pervanadate treatment or antibody cross‑linking of LMIR3 induces phosphorylation of tyrosine residues in the cytoplasmic domain and the subsequent recruitment of phosphatases SHIP, SHP-1, SHP-2, and the p85 alpha subunit of PI3K. LMIR3 ligation can induce cell death and inhibit signaling through multiple receptors including Fc epsilon RI, LMIR4, SCF R, TLR2, TLR3, and TLR9 . In contrast, it enhances TLR4‑mediated signaling/cytokine production in mast cells through association with the activating signaling protein FcR gamma. In mouse, a splice variant of LMIR3 (known as DIgR2, with a 7 aa insertion in the ECD) inhibits CD4+ T cell activation and in vivo Th1 and CTL responses. LMIR3 is up‑regulated on monocytes surrounding experimentally-induced spinal cord demyelination and functions as a negative regulator of inflammation in the CNS.