PDK2 (pyruvate dehydrogenase kinase 2) functions as a key metabolic regulator that inhibits the pyruvate dehydrogenase complex through phosphorylation, thereby controlling the switch between glucose and fatty acid metabolism 12. The enzyme operates within a regulatory network where it can be transcriptionally upregulated by c-Myc, forming feedback loops that sustain glycolytic metabolism in cancer cells 1. PDK2 demonstrates significant pathological relevance across multiple diseases, particularly in cancer and fibrotic conditions. In colorectal cancer, the OGT-c-Myc-PDK2 axis promotes tumor growth by suppressing TCA cycle metabolism and reducing reactive oxygen species production 1. In ovarian cancer, PDK2 phosphorylates transcription factor FOXK2, creating a positive feedback loop that sustains glycolysis and promotes malignancy 3. PDK2 also drives fibroblast proliferation in thyroid-associated ophthalmopathy through enhanced glycolysis via Akt signaling 2 and exacerbates orbital fibrosis in Graves' orbitopathy via IL11 signaling pathways 4. Clinically, PDK2 represents a promising therapeutic target, with inhibitors like dichloroacetic acid showing efficacy in reducing fibrosis and metabolic dysfunction 24. Additionally, PDK2 inhibition shows neuroprotective potential in ischemic stroke models 5, highlighting its broad therapeutic relevance across diverse pathological conditions.