TREM1 (triggering receptor expressed on myeloid cells 1) is a cell surface immunoregulatory receptor expressed on neutrophils, monocytes, and tissue macrophages 1. TREM1 functions as an inflammatory amplifier that, upon activation by damage- and pathogen-associated molecular patterns, initiates downstream signaling cascades resulting in pro-inflammatory cytokine and chemokine production 1. In the brain, TREM1 becomes upregulated in microglia following injurious stimuli and synergistically amplifies inflammatory responses, contributing to neurocognitive disorders including diabetes-associated cognitive impairment 2. In diabetes-associated cognitive impairment, impaired microglial lipophagy causes lipid droplet accumulation that colocalizes with TREM1, promoting neuroinflammatory cascades via NLRP3 inflammasome activation 3. Pharmacological TREM1 blockade reduces neuroinflammation and improves cognitive function 3. In cancer, TREM1 overactivation in tumor-infiltrating myeloid cells promotes tumor progression and immunosuppression by expanding immunosuppressive myeloid-derived suppressor cells and driving T cell exhaustion 4. TREM1 inhibition enhances anti-PD-1 immunotherapy efficacy 4. Genetically, rs2062323 polymorphism in TREM1 associates with reduced Alzheimer's disease risk 5. These findings establish TREM1 as a promising therapeutic target for inflammation-associated diseases including cancer and neurodegeneration.