Importantly, we explored a novel role of PGRN in maintaining mitochondrial homeostasis via PGRN-Sirt1-PGC-1α/FoxO1 signaling-mediated mitochondrial biogenesis and mitophagy in podocytes, suggesting that targeting mitochondrial function and cellular bioenergetics upstream of cellular damage by PGRN may provide unexpected opportunities for the treatment of DN. This evidence concerns the gene SIRT1 and liver dysplastic nodule.