Previous reports have consistently shown that tau seeds can be transported into lysosomes after neuronal internalization (15,18,62) and some linked lysosomal dysfunction to Tau aggregation (26,63). Our lab has previously shown that internalized tau aggregates can result in the subsequent rupture of unidentified vesicles in neurons (14), enabling tau seeds to promote tau aggregation in the cytosol. Now, our present work identified the lysosomal delivery of Tau seeds as a key step in the process of seeded Tau aggregation. Based on our **data** we hypothesize that by reducing the transport of tau seeds into lysosomes via PIKfyve inhibition, tau seeding can be halted. In line with this idea it has been recently shown that exosomes containing Tau seeds require transport into the lysosome as well as lysosomal rupture to promote Tau aggregation (64). Whereas tau-seeds-induced rupture of lysosomes has not been shown yet, other protein oligomers such as α-synuclein fibrils are known to induce rupture of the lysosomal compartment and induce seeding (65).