CD300e, originally termed immune receptor expressed by myeloid cells (IREM)-2, is a glycosylated surface receptor with a single extracellular Ig-like domain, belonging to a family of immune receptors that includes 8 members, either activating or inhibitory, that are expressed on myeloid cells, on lymphoid cells or on both compartments1. Since the ligand of CD300e is still unknown, its function in human cells has been studied by using an agonistic anti-CD300e monoclonal antibody2. The evidence that the engagement of CD300e in human monocytes and myeloid dendritic cells provided the cells with survival signals and triggered the expression of the activation markers and the release of pro-inflammatory cytokines, led to the conclusion that CD300e is an immune-activating receptor2. The presence of a lysine residue in the transmembrane domain suggested that CD300e might associate with an ITAM-containing adaptor molecule.