Notably, altered BA homeostasis has been proposed to play a central role in NAFLD pathophysiology and progression.3,5,6 Hydrophobic BAs, which can cause liver injury,7,8 are increased in the systemic circulation, hepatic tissue, and feces of patients with NASH.9–14 Although several drugs targeting the BA-activated nuclear receptor farnesoid X receptor (FXR/NR1H4) are currently in clinical development to treat NAFLD,15 the mechanistic causes of altered BA homeostasis during NAFLD development and progression remain largely unknown.5 This evidence concerns the gene NR1H4 and metabolic dysfunction-associated steatotic liver disease.