EDEM2 (ER degradation enhancing alpha-mannosidase like protein 2) is a key regulator of endoplasmic reticulum-associated degradation (ERAD) that targets misfolded glycoproteins for degradation 1. The protein functions by recognizing and binding to exposed hydrophobic regions in target proteins, with substrate recognition determined by sufficiently high hydrophobicity of protein determinants 2. EDEM2 initiates ERAD through mannose trimming of N-glycans and works alongside EDEM1 and EDEM3 to extract folding-defective proteins from the calnexin chaperone system 1. Beyond its canonical ERAD function, EDEM2 plays important roles in cellular homeostasis and disease. In cardiac tissue, EDEM2 regulates lipid homeostasis by facilitating ATGL-mediated triglyceride breakdown, with deficiency leading to lipid accumulation and heart failure with preserved ejection fraction 3. In pancreatic β-cells, EDEM2 silencing reduces insulin gene expression and secretion by suppressing glucose transporter and other endocrine-specific genes 4. EDEM2 overexpression is associated with poor prognosis in glioma and correlates with immune infiltration 5. Additionally, genetic variants in EDEM2 have been identified as risk factors for ACE inhibitor-induced angioedema 6, suggesting broader roles in drug metabolism and vascular biology.