In the current study, we demonstrate that PC1 contains a conserved RVxF motif, that PP1α interacts with and dephosphorylates PC1, and that PC1 mutations within the RVxF motif, including an ADPKD-associated mutation, block PP1α-mediated dephosphorylation. The gene discussed is PKD1; the disease is autosomal dominant polycystic kidney disease.