Fructosemetabolism predominantly relies on KHK due to its higher affinityfor fructose, and these findings alignwith previous studies demonstrating that genetic deletion or pharmacologicalinhibition of KHK protects against fructose-induced metabolic disorders,including NAFLD/NASH, type 2 diabetes, and cardiovascular disease. These findings highlight KHK as a key metabolic targetand establish AS-IV as a promising candidate for combating metabolicsenescence induced by excessive fructose intake. Here, KHK is linked to metabolic dysfunction-associated steatohepatitis.