Transforming growth factor-β-activated kinase 1 (TAK1) is a crucial central signaling molecule of hepatic cell death, inflammation and fibrogenesis through NF-κB and MAPK in metabolic dysfunction-associated steatotic liver disease (MASLD). Its pharmacological inhibition using the TAK1 inhibitor HS-276 was tested in vivo in a murine model of diet-induced MASLD.