Current understanding suggests that in high-grade (G3-G4) or late-stage (Stage III-IV) ccRCC, CHAC1 upregulation may represent a feedback adaptation response to the high intracellular glutathione environment, potentially indirectly promoting tumor progression by sustaining specific survival signals or resisting extreme oxidative stress (37, 38). This evidence concerns the gene CHAC1 and nonpapillary renal cell carcinoma.