Striking upregulation of KCNN4 expression in kidneys of all tested patients with ADPKD was recapitulated in all mechanistically distinct Pkd1 animal models examined, whether associated with loss of Pkd1 expression, partial Pkd1 loss of function, or Pkd1 overexpression. Here, KCNN4 is linked to autosomal dominant polycystic kidney disease.