Importantly, our results show that only the modulation of SIRT1 exerted by NorUDCA, but not the complete depletion (as in our hepatocyte‐KO mice), preserved FXR signaling and overall liver function after BDL, emphasizing the relevance of maintaining fine‐tuned SIRT1 expression to protect the liver during cholestasis. The gene discussed is SIRT1; the disease is cholestasis.