RNF13 (ring finger protein 13) is an E3 ubiquitin ligase that functions as a crucial regulator of multiple cellular processes including protein degradation, lysosomal positioning, and stress responses 1. The protein contains an N-terminal protease-associated domain and C-terminal RING finger domain separated by a transmembrane region, allowing it to localize to endosomal and lysosomal membranes 2. RNF13 mediates K48-linked polyubiquitination of target proteins, promoting their proteasomal degradation, as demonstrated with LAMP-1 at residue K128 1. The protein plays protective roles in pathological conditions by stabilizing the p62-mediated Nrf2/HO-1 signaling pathway, which is important in both cardiac hypertrophy and cerebral ischemia-reperfusion injury 34. RNF13 also regulates lysosomal positioning through pH- and Ca2+-dependent mechanisms, specifically by degrading ARL8B in response to elevated intracellular pH and Ca2+ signaling 5. Disease relevance includes developmental and epileptic encephalopathy 73 (DEE73), where variants L311S and L312P disrupt endosomal localization and AP-3 complex association 6. Additionally, RNF13 fusion proteins (RNF13::PAK2) have been identified in certain skin adnexal tumors 7, suggesting oncogenic potential in specific contexts.