KEY POINTS: Lack of BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in the METHODS: To disrupt the circadian clock, we deleted RESULTS: Human nephrectomy ADPKD kidneys showed altered clock gene expression when compared with normal control human kidneys. When compared with RC/RC kidneys, DKO kidneys showed significantly altered clock gene expression, increased cyst growth, cell proliferation, apoptosis, and fibrosis. DKO kidneys also showed increased lipogenesis and cholesterol synthesis–related gene expression and increased tissue triglyceride levels compared with RC/RC kidneys. Similarly, CONCLUSIONS: Renal collecting duct–specific