Abstract: Neurons are highly polarized, morphologically asymmetric, and functionally compartmentalized cells that contain long axons extending from the cell body. For this reason, their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal domains. Although some organelles, such as mitochondria and smooth endoplasmic reticulum, are widely distributed throughout the neuron, others are segregated to either the somatodendritic or axonal compartment. For example, Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon, whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon (Britt et al., 2016). To establish these polarized features, neurons regulate the axonal transport of organelles to maintain their distribution, integrity, and dynamics. Thus, it is not surprising that neurons in neurodegenerative diseases display early and diverse defects in organelle structure, distribution, and dynamics.