Accumulating evidence suggests that therapeutic AMPK activation (e.g., metformin, 2-deoxyglucose or dietary interventions) attenuates cystic kidney disease severity by inhibiting mTORC1, CFTR, inflammation/fibrosis, and restoring mitochondrial energy metabolism in Pkd1 mutant animal models (Takiar et al., 2011; Chiaravalli et al., 2016; Kipp et al., 2016; Riwanto et al., 2016; Warner et al., 2016; Leonhard et al., 2019; Lian et al., 2019; Torres et al., 2019; Pastor-Soler et al., 2022). Here, PRKAA2 is linked to cystic kidney disease.