By doing so, we observe that GABPA acts as a tumor suppressor by stimulating TGFBR2 transcription and TGFβ signaling, while the oncometabolite L-2-HG epigenetically inhibits GABPA expression, disrupting the GABPA-TGFβ loop to drive ccRCC aggressiveness. This evidence concerns the gene TGFBR2 and nonpapillary renal cell carcinoma.