Importantly, we also establish a mechanistic link between PSA-NCAM levels and GluN2B phosphorylation and trafficking, using both in vivo (AD and WT mouse brains) and in vitro (CRISPRa-ST8Sia4 overexpression) models to show that PSA-NCAM modulation directly regulates Ser1480 GluN2B phosphorylation and ES-GluN2B dynamics. The gene discussed is NCAM1; the disease is Alzheimer disease.