On the one hand, the TREM2 H157Y mutation, which is located directly at the TREM2 cleavage site, enhances TREM2 shedding, reduces cell surface TREM2, lowers TREM2-dependent phagocytosis, and is associated with late-onset AD (Jiang et al, 2016; Feuerbach et al, 2017; Schlepckow et al, 2017; Thornton et al, 2017; Fu et al, 2023; Qiao et al, 2023). Here, TREM2 is linked to Alzheimer disease.