VHL and cancer: VHL: VHL acts as a substrate recognition subunit of the E3 ligase complex, specifically targeting hypoxia-inducible factor 1α (HIF-1α) under normoxic conditions through UPS.52 HIF-1α, a transcription factor, primarily manages response to hypoxia, regulating processes such as erythropoietin synthesis, angiogenesis suppression, and cancer metastasis.53–55 The development of VHL ligands was guided by the structural analysis of VHL-HIF-1α interaction.