Systemic and portal hypertension, liver fibrosis, and hepatomegaly are manifestations associated with autosomal recessive polycystic kidney disease (ARPKD), which is caused by malfunctions of fibrocystin/polyductin. The goal is to understand how liver pathology occurs and to devise therapeutic strategies to treat it. We injected 5-day old Pkhd1del 3-4/del3-4 mice for one month with the CFTR modulator, VX-809, designed to rescue processing and trafficking of CFTR folding mutants (1). We used immunostaining and immunofluorescence techniques to evaluate liver pathology. We assessed protein expression via western blotting. We detected abnormal biliary ducts consistent with ductal plate abnormalities, as well as a greatly increased proliferation of cholangiocytes in the Pkhd1del 3-4/del3-4 mice. CFTR was present in the apical membrane of cholangiocytes and increased in the Pkhd1del 3-4/del3-4 mice, consistent with a role for apically located CFTR in enlarged bile ducts. Interestingly, we also found CFTR in the primary cilium, in association with PC2. Localization of CFTR and PC2 and overall length of the cilia were increased in the Pkhd1del 3-4/del3-4 mice. In addition, several of the heat shock proteins (27, 70, and 90) were upregulated, suggesting that global changes in protein processing and trafficking had occurred. We found that a deficit of FPC leads to bile duct abnormalities, enhanced cholangiocyte proliferation, and misregulation of heat shock proteins, which all returned toward wt. values following VX-809 treatment. These data suggest that CFTR correctors can be useful as therapeutics for ARPKD. Given that these drugs are already approved for use in humans, they can be fast-tracked for clinical use