RNF7 (ring finger protein 7) is a highly conserved E3 ubiquitin ligase component that functions as a catalytic element of cullin-RING ligase (CRL) complexes, particularly CRL5 complexes 1. In HIV infection, RNF7 participates in a cullin-5-RING E3 ubiquitin ligase complex hijacked by the HIV-1 Vif protein to ubiquitinate and degrade APOBEC3F and APOBEC3G antiviral proteins 2. Beyond viral contexts, RNF7 exhibits pleiotropic roles in cellular homeostasis. It functions as a mitochondrial ubiquitin ligase that promotes mitophagy independently of PRKN, directly ubiquitinating mitochondrial proteins and stabilizing PINK1 to maintain cardiac mitochondrial quality control 3. RNF7 possesses intrinsic anti-ROS capabilities and buffers against oxidative stress in glioma 4. In cancer, RNF7 is frequently overexpressed and promotes malignant progression: in prostate cancer, RNF7 is transcriptionally induced via the YTHDF1/m6A pathway, leading to p27 degradation and proliferation 2; in renal cell carcinoma, RNF7 ubiquitinates SOCS1, activating JAK/STAT3 signaling to inhibit apoptosis and promote glycolysis 5. RNF7 associates with PCNA, suggesting roles in DNA replication and repair 6. Genetic variants in RNF7 are associated with increased liver fibrosis and cirrhosis risk 7. In immune contexts, RNF7 components of CRL5 regulate IL-15R degradation in natural killer cells, with RNF7 ablation enhancing anti-tumor immunity 1. RNF7 upregulation occurs in inclusion body myositis, correlating with myofiber degeneration and protein aggregation 8.