Gankyrin-deficiency reprograms intrahepatic glucose and lipid metabolism to delay liver regeneration

• Gankyrin deficiency impairs liver regeneration after partial hepatectomy by disrupting glycogenolysis and fatty acid uptake. • Gankyrin promotes degradation of FOXO1 via ubiquitination, leading to upregulation of Pygl and Cd36 to fuel hepatocyte proliferation. • Pharmacological inhibition of PYGL activity retards liver regeneration, highlighting a potential therapeutic target. • The Gankyrin/FOXO1-PYGL/CD36 axis integrates metabolic reprogramming with proliferative signaling, offering novel strategies for enhancing liver regeneration in clinical settings.