Despite the favorable metabolic effects observed with exogenous administration of FGF21 analogs such as pegozafermin and zalfermin, which are currently under investigation for MASLD/MASH fibrosis, chronically elevated endogenous FGF21 may paradoxically reflect a state of resistance to FGF21 signaling [26,27]. Here, FGF21 is linked to metabolic dysfunction-associated steatotic liver disease.