KCNJ16-depleted kidney organoids recapitulate tubulopathy and lipid recovery upon statins treatment

• KCNJ16-depleted kidney organoids recapitulate key features of tubulopathy, including cysts, lipid droplet accumulation, and fibrosis. • Transcriptomic and metabolomic analyses reveal impaired voltage-dependent transporters and TCA cycle/lipid metabolism in KCNJ16−/− organoids. • Statin treatment, particularly simvastatin combined with C75, prevents lipid accumulation and collagen-I deposition, suggesting a potential therapeutic strategy. • This advanced in vitro model provides a platform for studying Kir5.1 function and testing interventions for KCNJ16-related kidney disease.