Triggering receptor expressed on myeloid cells 2 (TREM2) is a single Ig domain receptor expressed on macrophages and dendritic cells but not on granulocytes or monocytes. Its expression is most abundant in the basal ganglia, corpus callosum, medulla oblongata and spinal cord, and microglial cells are the major TREM2-producing cell type in the central nervous system. TREM2 may play a role in chronic inflammations and may stimulate production of constitutive rather than inflammatory chemokines and cytokines. TREM2 forms a receptor signaling complex with TYROBP and triggers activation of the immune responses in macrophages and dendritic cells. It also associates with the adapter protein DAP12 to deliver an activating signal that plays a role in both innate and adaptive immune responses. TREM2 signaling is also an important pathway to promote healing of wounds in the colon. TREM2 mutations increase the risk of neurodegenerative conditions such as Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease.