Synaptic vesicle glycoprotein 2A, the newly identified APP‐binding protein, reduces amyloid‐β plaque deposition in Alzheimer's disease by suppressing the amyloidogenic pathway through inhibition of BACE1‐APP interaction and alteration of APP endosomal‐lysosomal localization. Here, SV2A is linked to early-onset autosomal dominant Alzheimer disease.