SYVN1 (synoviolin 1) is an E3 ubiquitin ligase that functions as a central component of endoplasmic reticulum quality control through ER-associated degradation (ERAD) 1. Operating downstream of the UBC7 E2 ligase, SYVN1 ubiquitinates misfolded ER proteins, targeting them for proteasomal degradation and maintaining ER homeostasis 2. Beyond canonical ERAD, SYVN1 regulates diverse cellular processes through substrate-specific ubiquitination. It mediates degradation of transcription factors (p53, NFE2L1, ATF6) and metabolic enzymes (ACLY, MCT4), modulating cell survival, lipogenesis, and lactate metabolism 345. SYVN1 protects neurons from apoptosis induced by polyglutamine-expanded huntingtin and supports B cell differentiation by degrading pre-BCR complexes. Clinically, SYVN1 dysfunction is implicated in multiple pathologies: mutations cause ERAD-associated neurodevelopmental disorders; dysregulation promotes hepatocellular carcinoma, lung adenocarcinoma, and diabetic nephropathy through ferroptosis and EMT progression; and enhanced SYVN1 activity alleviates ischemia-reperfusion injury in liver and intestine 5678. These findings identify SYVN1 as a promising therapeutic target for cancer, metabolic, cardiovascular, and neurodegenerative diseases.