STK24 and obesity due to melanocortin 4 receptor deficiency: Proteomic profiling of MST3-deficient hepatocytes revealed coordinated activation of mitochondrial and lysosomal pathways, consistent with enhanced fatty acid degradation and catabolic clearance.<h4>Conclusions</h4>Our findings in the selected mouse model of MASH-HCC suggest that MST3 is dispensable for hepatocarcinogenesis, yet its antagonism dampens diet-induced metabolic dysfunction and effectively attenuates MASH severity, challenging the prevailing assumption that targeting MASH driver genes alone is sufficient to prevent HCC development in the context of obesity.