RNF31 (RING finger protein 31) is an E3 ubiquitin ligase that functions as a key component of the Linear Ubiquitin Chain Assembly Complex (LUBAC), which conjugates linear ('Met-1'-linked) polyubiquitin chains to target proteins 1. RNF31 plays critical roles in multiple cellular pathways through its ubiquitination activity. In autophagy regulation, RNF31 translocates to LC3 puncta areas during autophagy induction and mediates linear ubiquitination of ATG13, working cooperatively with OTULIN to control autophagy initiation and maturation 1. RNF31 demonstrates tissue-specific functions in cancer, acting as a tumor suppressor in triple-negative breast cancer (TNBC) by facilitating YAP polyubiquitination and degradation, thereby suppressing the Hippo/YAP/PD-L1 axis and enhancing immunotherapy sensitivity 2. However, RNF31 can also promote paclitaxel resistance in TNBC by ubiquitinating ALYREF and facilitating its nuclear transport 3. In inflammatory diseases, RNF31 contributes to pathogenesis through multiple mechanisms: it promotes NRF2 degradation via K63 ubiquitination in ulcerative colitis 4, mediates IKKα ubiquitination leading to enhanced NF-κB activation in neonatal necrotizing enterocolitis 5, and accumulates at damaged lysosomes to trigger local NF-κB activation and promote cell survival 6. These diverse functions highlight RNF31's central role in cellular homeostasis and disease pathogenesis.