Cumulatively, our findings revealed a new mechanism that the specific phosphorylation of nuclear YAP at its S127 and S397 sites mediated by CDK7 promotes LDHD transcription to drive D-lactate catabolism in the mitochondria, protecting esophageal CSCs from ferroptosis and generating pyruvate, finally supporting stem cell-like hallmarks of ESCC CSCs (Fig. 8k). Here, CDK7 is linked to esophageal squamous cell carcinoma.