TREM2 (triggering receptor expressed on myeloid cells-2) is a type I transmembrane microglial surface receptor that is found to be expressed on myeloid cells including monocyte-derived dendritic cells, osteoclasts and bone-marrow derived macrophage. TREM2 protein transduces intracellular signals that regulate microglial functions such as cytokine production, migration, proliferation, phagocytosis, cell survival, synapse elimination, and compaction of amyloid plaques^1,2.

The TREM2 structure includes an immunoglobulin-like extracellular domain responsible for ligand binding, a transmembrane region and a short cytoplasmatic tail. The protein also includes an ectodomain that binds anionic and zwitterionic lipids, apolipoproteins and lipoprotein particles^2,3.

Studies show that TREM2 knockout mice display decreased levels of inflammatory cytokines. TREM2 has been shown to control two signaling pathways in the brain: regulation of phagocytosis and suppression of inflammatory reactivity. Nasu-Hakola disease, a rare and fatal disease, and polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy has been found to be linked to homozygous loss-of-function mutations in TREM2 protein^1,2. Studies also show that variants of TREM2 are associated with Alzheimer’s disease^2,3.