 Proteostasis is important for maintaining healthy cells and preventing disease. It involves the regulation of protein folding and degradation, and when it is disrupted, can lead to age-related diseases. Molecular chaperones help to refold misfolded proteins, while other proteins such as alpha-2 macroglobulin, 2M, are involved in the lysosomal degradation of extracellular misfolded proteins. This study has identified the degradation pathway of 2M, which interacts with aggregation-prone proteins for lysosomal degradation via selective internalization. This article was authored by Ayaka Tomahari, Marko Piota, Akira Matsura, and others.