Mechanistically, multi-omics analysis identified PDHX as a key node within a broader metabolic network disrupted by TPL, associated with glycolytic suppression (<i>via</i> HK2 degradation) and mitochondrial dysfunction.<h4>Conclusion</h4>These findings suggest that TPL exerts antitumor effects in NSCLC by disrupting both glycolysis and mitochondrial function, with PDHX identified as a candidate mediator. This evidence concerns the gene HK2 and non-small cell lung carcinoma.