Autophagy is widely found in eukaryotic cells, and closely related to the physiological and pathological processes in the body. Autophagy-lysosomal pathway is a process of self-degradation of cells, mainly involved in the degradation of long-lived proteins to remove damaged or excessive protein and organelles. Autophagy is usually categorized into three groups: macroautophagy, chaperone-mediated autophagy, and microautophagy.Deficits in the ALP lead to protein aggregation, resulting in the accumulation of abnormal proteins and ineffective organelles, which are hallmarks of Alzheimer disease (AD), Parkinson disease (PD), Huntington disease (HD) and so on. The process of autophagy is regulated by a series of complex signaling molecules. One of them is TFEB, a member of the MiT family of transcription factors. Studies have shown that transcription factor EB (TFEB) can coordinate autophagy through positively regulating autophagosome formation and autophagosome- lysosome fusion. In addition, it enhances cellular clearance through lysosomal exocytosis. Therefore, as a major regulator of autophagosomal biogenesis, TFEB has been a key factor in the pathogenesis of related diseases. We reviewed the regulation of ALP and TFEB and their effects on neurodegenerative diseases, and looked forward to the complex effects of ALP and TFEB on pathology and their therapeutic significance.