VBP1 (VHL binding protein 1) is a multifunctional protein that primarily regulates protein stability and degradation pathways. The protein binds to the von Hippel-Lindau tumor suppressor protein (pVHL) and plays crucial roles in multiple cellular processes 1. VBP1 functions as a negative regulator of HIF-1α through dual mechanisms: it enhances pVHL-mediated ubiquitination and degradation of HIF-1α under normoxic conditions 2, and also promotes HIF-1α degradation through a pVHL-independent pathway involving the ubiquitin ligase CHIP and HSP70 3. Additionally, VBP1 modulates Wnt/β-catenin signaling by controlling the stability of TCF/LEF transcription factors, with both overexpression and knockdown leading to decreased signaling activity 4. The protein also regulates DNA repair mechanisms by facilitating proteasome and autophagy-mediated degradation of hMSH4, a meiotic recombination protein 5. VBP1 demonstrates tumor suppressor properties, as it inhibits cancer metastasis and epithelial-mesenchymal transition 2, though paradoxically promotes tumor proliferation in esophageal squamous cell carcinoma under hypoxic conditions 6. The gene is ubiquitously expressed across tissues with specific expression patterns in brain, eye, kidney, and intestine 7.