While previous studies have identified proliferative pathways such as mTOR and JAK/STAT as key regulators of proliferation in ADPKD, our study is the first to identify ANKHD1 as a direct regulator of the Cyclin D1/ CDK4/ p19 pathway, revealing a novel mechanism of cystic epithelial cell proliferation. Here, CDKN2A is linked to autosomal dominant polycystic kidney disease.