We conclude that EGLN1 represents a strong and selective vulnerability in tRCC, likely driven by a mechanism of HIF-1α stabilization that results in metabolic reprogramming away from OXPHOS and toward glycolysis, which is detrimental to tRCC cells (Fig. 3k). Here, EGLN1 is linked to renal cell carcinoma associated with Xp11.2 translocations/TFE3 gene fusions.