This bidirectional axis may explain TSGA10’s paradoxical roles in cancer: in thermosensitive tissues like the testis, its high expression could suppress HIF-1α to maintain OXPHOS and thermal stability, protecting against malignant transformation, whereas in thermally resilient tissues like the liver, low TSGA10 levels may permit HIF-1α-driven glycolytic reprogramming, facilitating tumorigenesis. The gene discussed is TSGA10; the disease is cancer.