Top, Neuronal function and survival depend on retrograde axonal transport driven by the microtubule motor protein dynein and its activator dynactin. Cargos that are actively transported along the axon include transport vesicles, mitochondria, lysosomes, autophagosomes, and signaling endosomes. Bottom, a significant slowing of retrograde axonal transport is observed at early stages of disease in several neurodegenerative models, consistent with a role in pathogenesis. This slowed transport leads to decreased flux, and potentially to defects in supply and clearance. MT: microtubules, oriented with plus (+) ends distal and minus (-) ends proximal to the cell body.