Proteins perform their functions when they fold in a correct 3D configuration; under stress conditions, they become misfolded and form toxic aggregates that could generate cell death. Our multidisciplinary research aims to use human in vitro cells, Caenorhabditis elegans, and several plant species to unveiling new mechanisms to degrade or repair aggregated/damaged proteins. Maintaining protein homeostasis (proteostasis) and avoiding toxic protein aggregation is relevant for extending healthy aging, delaying the development of neurodegenerative diseases, and designing the future varieties of stress-tolerant crops. We currently focus on unveiling proteostasis mechanisms that enable fungi to colonize plants successfully or activate cell-death responses.