Crumbs2 Is an Essential Slit Diaphragm Protein of the Renal Filtration Barrier

Significance Statement Mutations in the Crumbs2 ( CRB2 ) gene were recently identified as a cause of steroid-resistant nephrotic syndrome (SRNS), but it is unknown how Crumbs2 dysfunction damages the glomerular filtration barrier (GFB). Crumbs2 is a slit diaphragm protein, organized in clusters and able to interact with Nephrin. In mice, loss of Crumbs2 results in heavy proteinuria, accompanied by progressive podocyte foot process effacement,...