Enzymes, especially rate-limiting enzymes, determine the direction, strength, and speed of metabolic pathways; correlation analysis showed increased levels of glycolytic enzymes in SENP1 high-expression tumors, including PGK1, PFK1, ENO1, ALDOA, CA9, LDHA and HK2. Furthermore, SENP1 knockdown in RCC4/VHL cells noticeably reduced levels of key glycolytic enzymes under both normoxic and hypoxic conditions, providing evidence for SENP1 upregulation of glycolysis in ccRCC. This evidence concerns the gene HK2 and nonpapillary renal cell carcinoma.