Autophagy, a cellular process that degrades cytosolic components in lysosomes, plays a critical role in maintaining neuronal homeostasis and preventing neurodegenerative diseases. Dysfunction of autophagy has been linked to various neurodegenerative disorders, including Alzheimer's, Parkinson's, Huntington's, and Amyotrophic Lateral Sclerosis (ALS). The failure of autophagy in these diseases can arise from multiple steps in the autophagic process, and understanding these defects is essential for developing targeted therapies. Autophagy involves several pathways, including macroautophagy, microautophagy, and chaperone-mediated autophagy. Macroautophagy, which involves the formation of autophagosomes that fuse with lysosomes, is particularly important in neurons for clearing protein aggregates and damaged organelles. Defects in macroautophagy can lead to the accumulation of toxic proteins and organelles, contributing to neurodegeneration. The regulation of autophagy is complex, involving various proteins and signaling pathways, such as the mTOR pathway. Inhibition of mTOR can induce autophagy and reduce neurodegeneration in animal models. However, excessive autophagy can also be detrimental, as seen in some cases where autophagy inhibition improves neuronal survival. Autophagy failure can result from defects in cargo recognition, autophagosome formation, or clearance. For example, in Huntington's disease, impaired recognition of cargo by autophagosomes leads to inefficient degradation of toxic proteins. Similarly, defects in autophagosome clearance can lead to the accumulation of autophagosomes, which can interfere with intracellular trafficking and cause cytotoxicity. Recent studies have highlighted the importance of compensatory mechanisms between autophagy and other proteolytic systems, such as the ubiquitin-proteasome system. These interactions may provide alternative pathways for protein degradation and could be targeted for therapeutic intervention. Understanding the specific autophagic steps affected in different neurodegenerative disorders is crucial for developing effective therapies. Targeting autophagy modulation, enhancing cargo recognition, or improving autophagosome clearance could offer promising approaches for treating these diseases. Future research should focus on identifying the molecular mechanisms underlying autophagic dysfunction and exploring the potential of autophagy-related therapies in neurodegenerative disorders.Autophagy, a cellular process that degrades cytosolic components in lysosomes, plays a critical role in maintaining neuronal homeostasis and preventing neurodegenerative diseases. Dysfunction of autophagy has been linked to various neurodegenerative disorders, including Alzheimer's, Parkinson's, Huntington's, and Amyotrophic Lateral Sclerosis (ALS). The failure of autophagy in these diseases can arise from multiple steps in the autophagic process, and understanding these defects is essential for developing targeted therapies. Autophagy involves several pathways, including macroautophagy, microautophagy, and chaperone-mediated autophagy. Macroautophagy, which involves the formation of autophagosomes that fuse with lysosomes, is particularly important in neurons for clearing protein aggregates and damaged organelles. Defects in macroautophagy can lead to the accumulation of toxic proteins and organelles, contributing to neurodegeneration. The regulation of autophagy is complex, involving various proteins and signaling pathways, such as the mTOR pathway. Inhibition of mTOR can induce autophagy and reduce neurodegeneration in animal models. However, excessive autophagy can also be detrimental, as seen in some cases where autophagy inhibition improves neuronal survival. Autophagy failure can result from defects in cargo recognition, autophagosome formation, or clearance. For example, in Huntington's disease, impaired recognition of cargo by autophagosomes leads to inefficient degradation of toxic proteins. Similarly, defects in autophagosome clearance can lead to the accumulation of autophagosomes, which can interfere with intracellular trafficking and cause cytotoxicity. Recent studies have highlighted the importance of compensatory mechanisms between autophagy and other proteolytic systems, such as the ubiquitin-proteasome system. These interactions may provide alternative pathways for protein degradation and could be targeted for therapeutic intervention. Understanding the specific autophagic steps affected in different neurodegenerative disorders is crucial for developing effective therapies. Targeting autophagy modulation, enhancing cargo recognition, or improving autophagosome clearance could offer promising approaches for treating these diseases. Future research should focus on identifying the molecular mechanisms underlying autophagic dysfunction and exploring the potential of autophagy-related therapies in neurodegenerative disorders.