TREM2 (triggering receptor expressed on myeloid cells 2) is a membrane receptor exclusively expressed on microglia in the brain that plays a critical role in microglial activation and neurodegeneration 1. The primary function of TREM2 involves forming a signaling complex that mediates microglial responses including proliferation, survival, migration, and phagocytosis 2. TREM2 binds multiple ligands including amyloid-beta peptides, phospholipids, lipoproteins, and phosphatidylserine-expressing cells, promoting their uptake and clearance 3. The receptor signals through both SYK-dependent and SYK-independent pathways, with the SYK-dependent pathway being essential for microglial encasement of amyloid plaques and activation of the PI3K-AKT-mTOR pathway 4. TREM2 maintains microglial metabolic fitness by sustaining cellular energetic and biosynthetic metabolism, with deficiency leading to defective mTOR signaling and excessive autophagy 5. Disease relevance is significant, as TREM2 variants, particularly R47H, substantially increase Alzheimer's disease risk by impairing microglial function 6. Clinically, TREM2 represents a promising therapeutic target, with agonistic antibodies like AL002 showing safety and target engagement in phase 1 trials, demonstrating reduced soluble TREM2 in cerebrospinal fluid and enhanced microglial signaling 7.