In this study, we demonstrated that PKM2 serves as a cofactor in the regulation of CCN2 expression and may contribute to the progression of renal fibrosis by regulating YAP-TEAD and CCN2 expression in proximal tubular epithelial cells by forming transcriptional complexes of YAP1 and β-catenin. The gene discussed is CCN2; the disease is renal fibrosis.