Fructose-1,6-bisphosphatase 1 (FBP1) inhibits ccRCC progression through two distinct mechanisms: (1) by antagonizing glycolytic flux in renal tubular epithelial cells, thereby inhibiting a potential Warburg effect and (2) by restraining cell proliferation, glycolysis and the pentose phosphate pathway in a catalytic-activity-independent manner, by inhibiting nuclear HIF function via direct interaction with the HIF inhibitory domain. This evidence concerns the gene FBP1 and nonpapillary renal cell carcinoma.