METTLING in the pathogenesis of metabolic dysfunction-associated steatotic liver disease.

Metabolic dysfunction-associated steatotic liver disease (MASLD) progresses through distinct stages from hepatic lipid deposition or steatosis to metabolic dysfunction-associated steatohepatitis (MASH), and ultimately to cirrhosis or hepatocellular carcinoma (HCC). The pathogenesis of MASLD is dynamically regulated by epigenetic remodeling, among which the methyltransferase-like (METTL) family acts as a master regulator, coordinating multi-tiered pathological processes including modulating lipid homeostasis in hepatocytes, amplifying inflammatory signaling in Kupffer cells, driving fibrotic activation in stellate cells, and promoting malignant transformation via epigenetic reprogramming. By systematically deciphering the molecular interactome of the METTL family across hepatic cellular heterogeneity, this review aims to clarify hierarchical regulatory architecture governing the pathogenesis of MASLD and discuss precision epigenetic editing-based therapeutic paradigms.