Collectively, our studies for the first time demonstrate that PGRN protects against podocyte injury in DN, at least in part through maintaining mitochondrial homeostasis via PGRN- Sirt1-PGC-1α/FoxO1 signaling-mediated mitochondrial biogenesis and mitophagy (Fig. 8j), suggesting that PGRN may be an innovative therapeutic strategy for treating patients with DN. Here, PPARGC1A is linked to liver dysplastic nodule.