TREML1

TREML1 (Triggering Receptor Expressed on Myeloid Cells-Like 1), also known as TLT-1 or TREM-like transcript 1, is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. Predominantly expressed in myeloid-derived cells, including macrophages and microglia, it modulates innate immune responses by engaging with unidentified ligands to regulate inflammatory signaling. TREML1 interacts with adaptor proteins such as DAP12, activating downstream pathways including Syk kinase, PI3K/Akt, and NF-κB, which influence phagocytosis, cytokine release, and immune cell survival. Dysregulation of TREML1 has been implicated in neuroinflammatory disorders, notably Alzheimer’s disease, where it may exacerbate amyloid-β plaque accumulation by altering microglial activation states. Its role in atherosclerosis involves macrophage lipid metabolism and plaque stability.
Current drug development focuses on TREML1 as a therapeutic target for neurodegenerative and cardiovascular diseases. Preclinical studies explore monoclonal antibodies and small-molecule inhibitors to block its pro-inflammatory signaling. Notably, antisense oligonucleotides targeting TREML1 mRNA have shown efficacy in reducing neuroinflammation in animal models. However, clinical validation remains pending, with challenges including receptor-ligand specificity and off-target effects. Concurrent research investigates its diagnostic potential as a biomarker for disease progression in multiple sclerosis and systemic lupus erythematosus, leveraging its differential expression in activated immune cells.