We found that the expression of GCN5L1 is significantly elevated both in vivo in kidney tissues from DKD patients and mouse models and in vitro renal tubular epithelial cells (TECs) treated with high glucose, while reducing GCN5L1 expression could effectively attenuate mitochondrial oxidative stress, epithelial-to-mesenchymal transition (EMT), and inflammation induced by high glucose. This evidence concerns the gene BLOC1S1 and diabetic kidney disease.