MAPT and Alzheimer disease: Inhibiting PirB cleavage or overexpressing GGA3-GAT restored Golgi function, reduced Aβ plaque burden and tau phosphorylation, and rescued memory deficits.<h4>Conclusion</h4>Our study revealed a non-canonical pathway in which proteolytic cleavage repurposes PirB into an intracellular disruptor of Golgi trafficking, directly coupling immune receptor activation to organelle dysfunction in AD.