RNF183 is an endoplasmic reticulum (ER)-localized transmembrane E3 ubiquitin ligase that plays critical roles in cellular stress responses and disease pathogenesis 1. The protein catalyzes ubiquitin attachment to substrate proteins, with key functions in apoptosis regulation during prolonged ER stress through polyubiquitination and proteasomal degradation of anti-apoptotic proteins like BCL2L1 1. RNF183 expression is regulated by m6A RNA methylation, involving METTL3 and IGF2BP2, and this modification significantly impacts its cellular functions 2. In cancer contexts, RNF183 demonstrates tissue-specific roles: in lung adenocarcinoma, it promotes tumor progression by ubiquitinating SHP2 and activating STAT3 signaling 3, while in bladder cancer, it participates in glucose metabolism regulation through a YTHDC1/GLUT3/RNF183 feedback loop 4. The protein also targets metabolic enzymes like PKM2 for ubiquitination and degradation, affecting cellular energy metabolism 2. RNF183's activity is itself regulated by other ubiquitin ligases, such as FBXO5-mediated degradation, creating complex regulatory networks that control ER stress responses 5. These diverse functions make RNF183 a potential biomarker and therapeutic target in multiple diseases including cancers, diabetic nephropathy, and cardiovascular disease.