The most well-known and privileged ubiquitination-related enzyme of HIF-1α is pVHL E3 ubiquitin ligase, whose loss or inactivation can lead to the formation of tumors in multiple organs, such as hemangioblastomas of the brain, renal cysts and clear cell renal cell carcinoma, etc. [158]. The gene discussed is VHL; the disease is clear cell renal carcinoma.