TREM2 associates with the adaptor proteins DNAX activation protein 12 (DAP12) and DAP10 via oppositely charged residues in their transmembrane domains. Upon TREM2-ligand interaction, these co-receptors are phosphorylated and recruit intracellular signal transduction machinery. DAP12, also known as TYRO protein tyrosine kinase-binding protein (TYROBP), mediates activation of spleen tyrosine kinase Syk, whereas DAP10 promotes signal propagation by recruiting phosphatidylinositol 3-kinase (PI3K). TREM2 can bind DAP12 or DAP10 and possibly form TREM2-DAP12-DAP10 heterodimers. (32531244)