These data suggest that the phenotype of SPL mutations in vivo, which leads to steroid-resistant nephrotic syndrome, is due to the depressive effect of accumulating iS1P on WT1 and its target gene, nephrin, and that PKCδ is a key protein kinase, contributing to the pathology, and that selective inhibitors of PKCδ should be considered as a target for the pharmacological treatment of a steroid-resistant nephrotic syndrome induced by SPL mutations. Here, SGPL1 is linked to nephrotic syndrome.