Our findings suggest a model by which SMPDL3b may affect podocyte function and survival, where excessive SMPDL3b expression may cause the displacement of IR from caveolin-1-rich domain in a C1P-dependent manner, resulting in impaired ability to phosphorylate AKT thus promoting podocyte injury in vitro and development of DKD in vivo. This evidence concerns the gene SMPDL3B and diabetic kidney disease.