[Isoform 1]: Cell surface receptor that plays important roles in innate and adaptive immunity by amplifying inflammatory responses (PubMed: 10799849, PubMed: 21393102). Upon activation by various ligands such as PGLYRP1, HMGB1 or HSP70, multimerizes and forms a complex with transmembrane adapter TYROBP/DAP12 (PubMed: 25595774, PubMed: 17568691, PubMed: 29568119). In turn, initiates a SYK-mediated cascade of tyrosine phosphorylation, activating multiple downstream mediators such as BTK, MAPK1, MAPK3 or phospholipase C-gamma (PubMed: 21659545, PubMed: 14656437). This cascade promotes the neutrophil- and macrophage-mediated release of proinflammatory cytokines and/or chemokines, as well as their migration and thereby amplifies inflammatory responses that are triggered by bacterial and fungal infections (PubMed: 17568691, PubMed: 17098818). By also promoting the amplification of inflammatory signals that are initially triggered by Toll-like receptor (TLR) and NOD-like receptor engagement, plays a major role in the pathophysiology of acute and chronic inflammatory diseases of different etiologies including septic shock and atherosclerosis (PubMed: 21393102, PubMed: 11323674). [Isoform 2]: Acts as a decoy receptor, counterbalancing TREM1 proinflammatory activity through the neutralization of its lignad.
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