Recurrence of focal segmental glomerulosclerosis (FSGS) post-transplant can be dramatic and lead to graft loss. Several years ago, a “permeability factor” was discovered that seemed to cause recurrence, and could be removed by plasma exchange. However, until now, the nature of this factor has been unknown. In this set of experiments, the authors show that a soluble form of the podocyte urokinase receptor (suPAR) is found in high levels in patients with recurrent FSGS post-transplant. They also demonstrate that in vitro and in mouse models that suPAR can cause proteinuria and change of FSGS.