In the context of CF-related polycystic liver disease (PLD), Spirli et al. (2017) utilized a Pkd2-knockout mouse model to generate biliary organoids and demonstrated that adenylyl cyclase 5 (AC5) promotes cyst-like structure overgrowth through activation of the cAMP/ERK signaling pathway. Here, ADCY5 is linked to cystic fibrosis.