The spectrum of Metabolic dysfunction–associated steatotic liver disease (MASLD) encompasses different abnormalities, ranging from a simple steatosis to metabolic dysfunction–associated steatohepatitis (MASH) with various degrees of inflammation, ballooning, necrosis, fibrosis, and ultimately, cirrhosis and hepatocellular carcinoma. The heterogeneity of the diseases and its complex pathophysiological mechanisms represent a challenge to defining potent drugs for all patients with MASH. Delineating the mechanisms underlying the pathogenesis of MASLD is crucial to managing MALSD and its comorbidities obesity and type 2 diabetes mellitus.