UBXN7 (UBX domain protein 7) is a multifunctional adapter protein that coordinates ubiquitin-mediated protein degradation and cellular stress responses. Its primary function involves linking cullin-RING ligases (CRLs) to the p97/VCP segregase complex to regulate substrate turnover 1. UBXN7 operates through multiple mechanisms: it directly binds neddylated cullins via its UIM motif, independently of ubiquitin binding 2, and reduces the ubiquitin threshold required for p97-UFD1-NPL4 unfoldase activity, facilitating efficient substrate unfolding 3. The protein serves as a scaffold for both CRL3KEAP1 and CRL2VHL complexes, reciprocally regulating NRF2 and HIF-1α transcription factors in response to oxidative stress and hypoxia 1. UBXN7 is essential for DNA replication termination, participating in replisome disassembly through CUL2LRR1-driven MCM7 ubiquitylation 4. Disease relevance includes its role in viral replication, where it stabilizes SARS-CoV-2 N protein by inhibiting K48-linked ubiquitination 5, and in hepatitis B infection, where HBx protein induces UBXN7 degradation to activate NF-κB signaling 6. Additionally, UBXN7 shows potential as a diagnostic biomarker in pulmonary hypertension 7.