The TREM2 His157Tyr mutation presents a complex and contradictory profile in neurodegenerative disease research, evidenced by its association with accelerated TREM2 protein shedding and AD risk, yet simultaneously exhibiting potential beneficial effects on synaptic plasticity and reduced amyloid pathology, with varying impacts across different patient populations [149,150,151,152,153,154]. Here, TREM2 is linked to neurodegenerative disease.