 The ubiquitin proteasome system, UPS, plays a key role in the development of membranous nephropathy, MN. Autoantibodies targeting podocytes lead to protenuria, and oxidative stress causes the induction of the enzyme UCH-L1 in these cells. This enzyme then interacts with and impairs the proteasome, leading to increased accumulation of proteins and further damage to the podocytes. In MN patients with poor outcomes, antibodies against non-functional UCH-L1 are more prevalent than those against functional UCH-L1. Furthermore, deleting UCH-L1 in podocytes prevents MN, while overexpressing non-functional UCH-L1 leads to podocyte dysfunction and injury in mice. These findings suggest that the UPS is involved in the pathogenesis of MN through its interaction with non-functional UCH-L1. This article was authored by Julia Weichelt, Weebke Sachs, Sarah Frumbeling, and others. We are article.tv, links in the description below.