ONLINE COVER Endoggresomes, which are toxic to nerve cells, form within nerve fibers. These swellings are common features of neurodegenerative diseases, including rare, inherited forms of prion diseases—disorders that cause rapidly developing dementia, severe disability, and death. Chassefeyre et al. identified the toxic pathway of endoggresomes as it forms along microtubules and moves into the axon. The research could lead to targeted therapeutic strategies to reduce the formation of toxic endoggresomes and, in turn, to prevent neuronal dysfunction.