Genetic data accumulated over the last decade indicate that defects in protein and organelle protein quality control pathways underlie many types of neurodegenerative diseases, including Parkinson’s, ALS, and Alzheimer disease. Central to these quality control systems is a process called autophagy, wherein damaged proteins, protein aggregates and organelles are captured within a sub-cellular structure referred to as an autophagosome and delivered to the lysosome. The lysosome contains a number of proteases that convert the damaged proteins and organelles into amino acids, which can be re-used for production of new proteins. Our work focuses on several genes mutated in Parkinson’s disease and ALS that mark damaged proteins and organelles such as mitochondria (referred to as “cargo”) with a protein tag called ubiquitin and that recognize ubiquitylated cargo and deliver it to the autophagosome. We study the biochemistry and cell biology of these pathways in order to understand how cargo is marked with ubiquitin and how such ubiquitylated cargo is recognized. In addition, we are developing embryonic stem cells harboring mutations in key genes created by gene editing, and are using these resources to create various types of neurons, allowing us to examine the functions of these important genes in quality control in relevant cell types using biochemical and imaging-based approaches. Our studies are revealing an intricate series of steps that dictate how damaged organelles are initially recognized as defective, the individual steps in marking such organelles, and how “autophagy receptors” couple damaged organelles to the auto-lysosomal system.