TheTREM2–DAP12 interaction is initiated through electrostaticpairing between lysine 186 (K186) of TREM2 and conserved aspartateresidues (D50) in DAP12, forming a stable trimeric transmembrane complex. Additional stabilization is provided by W194in TREM2, which forms a hydrogen bond with T54 in DAP12. While most functional studies of TREM2 focuson extracellular domain mutations, emerging evidence implicates transmembranedomain variants in AD risk. The gene discussed is TREM2; the disease is Alzheimer disease.