Focal segmental glomerulosclerosis (FSGS) is a progressive and devastating glomerular disease and a major glomerular reason for end stage renal disease. It is hypothesized that primary FSGS is caused by an unknown circulating (immune) factor, which leads to podocyte injury and disease recurrence after kidney transplantation. In the previous funding period, we established (1) a well-defined patient cohort suffering from an early recurrence of FSGS after kidney transplantation, (2) novel in vitro and in vivo FSGS models, (3) single nucleus analysis pipelines of kidney biopsies and (4) in silico tools for the analysis of multi-omics datasets to unravel novel FSGS-associated regulatory networks. Based on our findings, we now aim to (1) systematically integrate the multi-omics datasets obtained from all models mentioned above; (2) characterize and validate identified common and novel FSGS pathways and circulating factor(s); and (3) implement a pipeline for systematic drug repurposing. Together, this project will facilitate FSGS pathway and treatment discovery and shall exemplify a generalizable translational glomerular disease strategy.