Neural cells are unique in both their size and function: in humans, they can extend up to 1m long and survive for more than 80 years. To maintain health over this size and lifetime, new proteins and organelles must be supplied to distant regions and molecular debris cleared from the entire cell continuously. The molecular motors dynein and kinesin shuttle materials throughout the cell to ensure homeostasis between production and degradation is maintained. A specialized organelle called the autophagosome is responsible for much of the degradation in neurons. Autophagosomes envelop dysfunctional proteins and organelles in a membrane and subsequently degrade the cargo inside. Neuronal autophagosomes form in the distal axon and are transported by dynein to the soma, where most of the protein and organelle production occurs. During my thesis work, I investigated mechanisms underlying axonal autophagy. I identified the regulatory proteins responsible for activating dynein on axonal autophagosomes and examined the spatial and temporal dynamics of axonal autophagosome maturation. I found four proteins, Huntingtin-associated protein 1 (HAP1) and Jnk-interacting proteins (JIPs) 1, 3, and 4, that regulate dynein on axonal autophagosomes in a sequential pattern. JIP1 inactivates kinesin on nascent autophagosomes to initiate their axonal transport out of the axon tip. HAP1 and its partner Huntingtin (mutated in Huntington’s disease) then activate dynein on partially mature autophagosomes along the middle of the axon. Finally, JIP3 and JIP4 activate dynein on mature autophagosomes (autolysosomes) as they approach the soma. I identified a novel motif in multiple families of dynein effectors, including HAP1 and JIP3/4, that allow these effectors to bind dynein’s partner complex dynactin. Additionally, I assisted in the identification of a structurally conserved mechanism by which dynein effectors interact with dynein. Lastly, I collaborated to computationally model the interplay between autophagosomal transport and maturation along the axon, which allowed us to identify rate-limiting steps in the degradation of autophagic cargo. Together, these studies provide invaluable insight into autophagy and axonal transport, both of which are dysfunctional in neurodegenerative and neurodevelopmental diseases.