RNF39 (ring finger protein 39) is an E3 ubiquitin ligase that regulates multiple cellular processes through protein ubiquitination. The protein functions primarily through K63-linked ubiquitination to promote STING activation in antiviral immune responses 1. RNF39 interacts with STING in macrophages and facilitates formation of the STING-TBK1 complex, accelerating DNA-sensing pathways crucial for innate immunity 1. Additionally, RNF39 promotes HIV-1 replication, as genetic variants associated with lower RNF39 expression correlate with reduced viral loads in patients 2. In cancer, RNF39 acts as an oncogenic factor by targeting RINT1 for K48-linked polyubiquitination and proteasomal degradation, thereby suppressing ER stress-induced apoptosis and promoting colorectal cancer progression 3. The gene is upregulated by transcription factor MEF2D and its high expression correlates with poor patient survival 3. RNF39 is located within the MHC class I region and has been associated with Behçet's disease independently of HLA alleles 4. The protein represents a potential therapeutic target for viral infections and cancer, given its dual roles in immune regulation and oncogenesis.