Triggering Receptor Expressed on Myeloid cells 2 (TREM2)is a 35 kDa type I transmembrane member of the TREM family and Ig superfamily. Mature human TREM2 consists of a 156 amino acid (aa) extracellular domain (ECD) with one V-type Ig-like domain, a 21 aa transmembrane (TM) domain, and a 35 aa cytoplasmic tail. Soluble forms of the TREM2 ECD are generated by alternative splicing or proteolytic cleavage, and the cytoplasmic domain can be liberated by gamma-Secretase mediated intramembrane cleavage. A positively charged lysine within the transmembrane segment allows association with the signal adapter protein, DAP12 and inhibition of macrophage activation. TREM2 is expressed on macrophages, immature myeloid dendritic cells, osteoclasts, microglia, and adipocytes.It promotes the differentiation and function of osteoclasts, the production of inflammatory cytokines by adipocytes, insulin resistance, and the phagocytic clearance of bacteria.