Since some, but not all, cyst-lining epithelial cells in ADPKD renal tissue showed increased nuclear GLI1 staining, and increased Gli1 transcripts have been evident in kidneys of mouse models that were already cystic14,22,23, we speculate that Hh signaling may increase with disease progression, and that patients with more advanced ADPKD might show a greater increase in Hh signaling than those with earlier disease. Here, GLI1 is linked to autosomal dominant polycystic kidney disease.