Despite our kidney organoid models are not compatible with direct measuring of intracellular potassium, our results show that total loss of Kir5.1 (KCNJ16) led to transcriptomic impairment of key transporters regulating essential cellular homeostasis and metabolic processes, which resulted in pH imbalance, cyst formation and metabolic landscape impairment, with particular impact on the TCA cycle and lipid metabolism. The gene discussed is KCNJ16; the disease is cyst.