Extracellular ligand-pseudokinase axis rewires lipid metabolism in steatohepatitis.

Metabolic dysfunction-associated steatohepatitis is traditionally viewed as a hepatocyte-autonomous metabolic disorder. A recent study by Xi et al. identifies a soluble glycoprotein nonmetastatic melanoma protein B ectodomain that activates the pseudokinase receptor tyrosine kinase to drive ERK-dependent lipogenesis, revealing an extracellular mechanism that instructs hepatic metabolism and highlighting a potential therapeutic target.