Abstract: Lysosomes are ubiquitous and dynamic organelles with a central role in degradation and recycling of damaged cell components and misfolded proteins, otherwise known as autophagy. Autophagy plays a fundamental role in the process of correcting cell homeostasis and cellular survival. Unsurprisingly, this process is essential in the central nervous system, as neurons are not able to easily eliminate altered proteins given their post-mitotic state. Thus, lysosomal function is critical in maintaining neuronal health. Interestingly, increasing evidence suggests that impaired autophagy underlies several neurodegenerative diseases. Genetic deletion of key components of the autophagy machinery results in the accumulation of protein aggregates and subsequent neuropathologies. Moreover, some genetic variants found in lysosomal storage disorders (LSDs), which can also be hallmarked by neuronal degeneration, have been implicated as risk factors for Alzheimer’s disease (AD), Parkinson’s disease (PD) and others. Specifically, deficiency in the cathepsin family of lysosomal proteases, which play a vital role in the clearance of aggregation-prone proteins, such as alpha-synuclein (αSyn), amyloid β peptide, and saposins C (SapC) and D (SapD), seems to contribute to neuropathogenesis. Hence, targeting lysosomal function represents a novel therapeutic approach for tackling neurodegeneration.