Glis2 inactivation is effective in reducing polycystic kidney disease progression in adult models based on both Pkd1 and Pkd2. The Pkd genotype-dependent changes in Glis2 transcription and protein expression have a causative role in progression of polycystic kidney disease that can be ameliorated by inactivation of the Glis2 gene. Here, PKD2 is linked to polycystic kidney disease.