In this study, for the first time, we addressed these questions in an in vitro model of cholestasis using a bile acid-treated human hepatoma HepG2 cell line and in vivo using a bile-duct ligation (BDL) experimental model of cholestasis with Sestrin2 wild-type (Sesn2+/+) and knockout (Sesn2−/−) mice. Here, SESN2 is linked to cholestasis.