TREM2

Class

TREM2 agonist/activator

TREM2 (Triggering Receptor Expressed on Myeloid Cells 2) is a cell-surface receptor found predominantly on microglia, the resident immune cells of the brain, and on macrophages elsewhere in the body. It senses lipids and lipid-associated debris released by damaged cells, including material shed from amyloid plaques and degenerating myelin. Engagement of TREM2 triggers intracellular signaling that supports microglial survival, proliferation, migration toward sites of injury, and phagocytic clearance of debris. Genetic studies have shown that people carrying loss-of-function variants in TREM2 have a substantially higher risk of Alzheimer's disease, indicating that robust TREM2 signaling helps microglia perform a protective, house-keeping role in the aging brain. This has made TREM2 an attractive target for agonist therapies intended to boost microglial function in neurodegenerative disease, particularly Alzheimer's disease, where enhancing debris clearance and limiting neuronal damage could slow disease progression. TREM2 agonism is being pursued through both small-molecule activators and agonist antibodies, reflecting different strategies for engaging the same receptor while managing brain penetration and dosing requirements. Because TREM2 signaling also shapes macrophage behavior in tissues such as bone and liver, modulating it carries considerations beyond the central nervous system.