Diverse neurodegenerative diseases share a common cause: aggregation of a specific protein in selective regions of the brain. The disease-causing proteins are expressed throughout life but neurodegenerative diseases are mostly late-onset. In fact, cells normally strive to ensure that proteins get correctly folded and indeed all cells have powerful and sophisticated protein quality control systems that very efficiently handle potentially harmful proteins for decades. However, the protein quality control mechanisms seem to gradually fail with age, leading to the accumulation of misfolded proteins with the resulting catastrophic consequences for cells and organisms. My long-term goal is to understand the mechanisms that govern the deposition of misfolding-prone proteins, why they persist in aged cells and to identify strategies that could reduce the burden of misfolded proteins for cells and organisms.