Inactivation of Glis2 suppressed cyst formation in two early onset models of ADPKD based on Pkd1 and two adult models based on either Pkd1 or Pkd2. The protection in the adult inducible model of Pkd1 was particularly complete and could be interpreted in the absence of confounding by the nephronophthisis phenotype that occurs in germline Glis2−∕− mice. Here, PKD2 is linked to nephronophthisis.