Autophagy is a critical cellular process that maintains homeostasis by degrading and recycling cellular components, including damaged proteins and organelles. It plays a vital role in the nervous system, where it is essential for neuronal development, function, and survival. Mutations in autophagy-related genes are linked to various neurodevelopmental and neurodegenerative disorders. This review discusses the regulation of autophagy, its spatial compartmentalization in neurons, and its implications in health and disease. Autophagy is regulated by a complex cascade involving multiple proteins, including ATG proteins. The process begins with the formation of autophagosomes, which are then transported to lysosomes for degradation. In neurons, autophagy is particularly important due to their post-mitotic nature and polarized structure. Neurons require efficient autophagy to manage toxic components and maintain homeostasis. Autophagy is regulated in different neuronal compartments, including the axon, soma, and dendrites, with distinct mechanisms and functions in each. In the axon, autophagosome biogenesis occurs at the distal end, and maturation is facilitated by retrograde transport to the soma. Autophagosomes are then degraded in the soma, where lysosomes are concentrated. In the soma, autophagosomes are primarily formed from the axon, and their degradation is supported by the presence of degradative lysosomes. In dendrites, autophagy is influenced by neuronal activity, with synaptic activity promoting autophagosome biogenesis and transport. Dendritic autophagosomes are often bidirectionally transported and can be rapidly degraded upon fusion with lysosomes. Mutations in autophagy-related genes have been implicated in various neurological disorders, including Parkinson's disease, Alzheimer's disease, and spinocerebellar ataxia. These mutations disrupt autophagy, leading to the accumulation of toxic proteins and organelles, which contribute to neuronal dysfunction and disease progression. Understanding the regulation and compartmentalization of autophagy in neurons is crucial for developing therapeutic strategies to treat neurodegenerative diseases.Autophagy is a critical cellular process that maintains homeostasis by degrading and recycling cellular components, including damaged proteins and organelles. It plays a vital role in the nervous system, where it is essential for neuronal development, function, and survival. Mutations in autophagy-related genes are linked to various neurodevelopmental and neurodegenerative disorders. This review discusses the regulation of autophagy, its spatial compartmentalization in neurons, and its implications in health and disease. Autophagy is regulated by a complex cascade involving multiple proteins, including ATG proteins. The process begins with the formation of autophagosomes, which are then transported to lysosomes for degradation. In neurons, autophagy is particularly important due to their post-mitotic nature and polarized structure. Neurons require efficient autophagy to manage toxic components and maintain homeostasis. Autophagy is regulated in different neuronal compartments, including the axon, soma, and dendrites, with distinct mechanisms and functions in each. In the axon, autophagosome biogenesis occurs at the distal end, and maturation is facilitated by retrograde transport to the soma. Autophagosomes are then degraded in the soma, where lysosomes are concentrated. In the soma, autophagosomes are primarily formed from the axon, and their degradation is supported by the presence of degradative lysosomes. In dendrites, autophagy is influenced by neuronal activity, with synaptic activity promoting autophagosome biogenesis and transport. Dendritic autophagosomes are often bidirectionally transported and can be rapidly degraded upon fusion with lysosomes. Mutations in autophagy-related genes have been implicated in various neurological disorders, including Parkinson's disease, Alzheimer's disease, and spinocerebellar ataxia. These mutations disrupt autophagy, leading to the accumulation of toxic proteins and organelles, which contribute to neuronal dysfunction and disease progression. Understanding the regulation and compartmentalization of autophagy in neurons is crucial for developing therapeutic strategies to treat neurodegenerative diseases.