The connection of defective protein turnover and irreversible podocyte disease is conserved among species. We could show that the proteasome system orchestrates proteostasis and endocytosis of healthy podocytes. Upon autoimmune injury, the turnover of the membranous nephropathy (MN) antigen THSD7A is altered in a proteasome-dependent manner. In this setting we identified an injury-related hotspot of immunoproteasomal degradation at footprocesses, which modifies podocyte protein abundance and ectosome formation. Hence, we hypothesize that the proteasome system is a common modifier of podocyte disease progression, severity, and outcome. The overall goal of this project is to unravel the functional role of the (immuno)proteasome at footprocesses in MN. We will characterize 1) the mechanisms connecting the proteasome system with podocyte plasma membrane dynamics using Drosophila melanogaster; 2) the pathomechanistic function of immunoproteasomal degradation for footprocess proteostasis and remodeling in experimental mammalian models of MN and 3) the potential of glomerular and urinary MN-associated ectosomes in the prediction of MN severity and outcome. Collectively, our results will demonstrate, if the immunoproteasome-dependent formation of MN-associated ectosomes in podocytes represents a general pathophysiologic concept with therapeutic and prognostic value in membranous nephropathy.