RNF130 (ring finger protein 130) is an E3 ubiquitin-protein ligase that plays diverse roles in cellular regulation and disease pathogenesis. As a member of the PA-TM-RING-type transmembrane E3 ligase family, RNF130 facilitates ubiquitin-dependent protein degradation and can be targeted for therapeutic protein degradation strategies 1. The protein demonstrates significant involvement in tau protein homeostasis, where its knockdown reduces tau levels and rescues disease phenotypes in tauopathy mouse models, suggesting therapeutic potential for Alzheimer's disease and related disorders 2. In multiple myeloma, RNF130 serves as the host gene for tumor suppressor miR-340-5p, with promoter methylation leading to silencing of both RNF130 and miR-340-5p expression, correlating with poor patient survival 3. Recent studies identify RNF130 as overexpressed in triple-negative breast cancer, where it promotes tumor progression through TNF-α pathway activation and contributes to immune evasion 4. Additionally, RNF130 functions in lipid metabolism by regulating low-density lipoprotein receptor degradation 5. Genetic variants in RNF130 are associated with sarcopenic obesity susceptibility 6, and the gene shows SOX10-mediated regulation in enteric glial cells with potential relevance to multiple sclerosis 7.