Multiple signaling pathways converge to orchestrate the profound metabolic reprogramming observed in cystic epithelial cells in ADPKD, including the cAMP/PKA axis, PI3K/Akt/mTORC1 signaling, Ras/ERK-induced c-Myc activation, mitochondrial dysfunction–induced HIF-1α stabilization, and NRF2 suppression. The gene discussed is AKT1; the disease is autosomal dominant polycystic kidney disease.