(A) In normal cholangiocytes, ciliary signaling results in increased levels of intracellular Ca2+, p21/WAF1, EGFR (in the cell membrane), and nuclear ID2 (10). These and/or other events result in miR15a expression and CDC25A repression. Decreased levels of CDC25A then lead to G1 arrest, preventing cyst formation. (B) As demonstrated in this issue of the JCI by Lee and colleagues (7), miR15a levels are reduced in PCK rat cholangiocytes and in ARPKD, CHF, and ADPKD liver specimens. In the PCK rat, ARPKD, and CHF, the PKDH1 gene is mutated [mutPKDH1], while in ADPKD, either PKD1 or PKD2 is mutated. CDC25A levels are increased in these same tissues. Using antisense oligonucleotide knockdown of miR15a in rat cholangiocytes, Lee and colleagues confirmed that reduction of miR15a results in elevated Cdc25A levels, increased cell proliferation, and cyst growth in vitro, while overexpression of miR15a in PCK cholangiocytes has the opposite effect.