PRNP and prion disease: By modeling the formation of intra-axonal mutant PrP aggregates involved in human prion disease (24), we uncovered endolysosomal pathways in mammalian neurons that sort post-Golgi mutant PrP vesicles into two divergent itineraries: one for immediate lysosomal degradation in the soma in a process resembling RESET (21, 22), and the other toward the axon by an Arl8b/kinesin-1/HOPS ARESTA axis that ensures their axonal entry, fusion, and aggregation inside endolysosomes that we call endoggresomes (fig.