CLDN4 and autosomal dominant polycystic kidney disease: In developing a hypothesis for Pkd1 action, we considered the fact that mechanistically, Pkd1 loss in ADPKD produces cysts in part by upregulating claudins 4 and 7 (CLDN4, CLDN7) and others that similarly induce impermeable tight junctions, while downregulating those that permit barrier permeability [46, 47].