AD-associated TREM2 risk variants – including p.H157Y, p.R98W, p.D87N, p.T66M, p.R62H, p.R47H, p.Y38C and p.Q33X [6, 43] – affect TREM2 function by various mechanisms, such as reduced ligand binding (p.R47H [96], p.R62H [97]), reduced cell surface expression (p.T66M [98]), and increased shedding (p.H157Y [45], Table 1). The gene discussed is TREM2; the disease is Alzheimer disease.