TREM-2 (Triggering Receptor Expressed on Myeloid cells-2) is a transmembrane protein that is expressed on newly differentiated and alternatively activated tissue macrophages, immature myeloid dendritic cells, and osteoclasts. TREM-2 interacts with and modifies signaling through dendritic cell and osteoclast Plexin A1, a semaphorin receptor. It is active in several settings that involve membrane fusion, including phagocytosis of microbes by macrophages and apoptotic neurons by microglia, and formation of osteoclasts and multinucleated giant cells from macrophages. TREM-2 signals through the adaptor protein DAP12 and can associate with the linker protein LAT2 to inhibit macrophage activaation. A soluble isoform of TREM-2 antagonizes full-length TREM-2 and is elevated in cerebrospinal fluid of patients with active multiple sclerosis.