In recent years, multiple studies have demonstrated that S100A8/A9 plays critical roles in cardiomyocyte death, mitochondrial dysfunction, and epithelial-to-mesenchymal transition (EMT) during the progression of cardiovascular diseases, such as MI, myocardial I/R injury, organ fibrosis, and diabetic nephropathy, through binding to toll-like receptor 4 (TLR4) or the receptor for advanced glycation end products (RAGE) 10-15. The gene discussed is TLR4; the disease is diabetic kidney disease.