The present study showed that podocyte-specific Crb2 knockout mice developed massive albuminuria and microhematuria at 2 months of age, FSGS with tubulointerstitial fibrosis at 6 months of age, and that podocyte-specific deficiency of CRB2 was associated with segmental foot process effacement, significant downregulation of slit diaphragm-associated proteins (Nphs1, Nphs2), apical membrane protein (Podxl) and decreased number of glomerular Wt1-positive cells compared to their negative control counterparts. Here, NPHS1 is linked to focal segmental glomerulosclerosis.