Selenoprotein M (SELENOM) is a selenocysteine-containing protein with oxidoreductase activity that functions primarily as a thiol-disulfide isomerase in the endoplasmic reticulum 1. Its catalytic mechanism relies on a thioredoxin motif containing both cysteine and selenocysteine residues 2, enabling enhanced redox activity compared to cysteine alone 1. SELENOM regulates cellular redox homeostasis and protects against oxidative stress across multiple tissues 1. In adipose tissue, SELENOM deficiency impairs antioxidant capacity, reducing NADPH and glutathione levels, thereby promoting reactive oxygen species (ROS) accumulation and triggering metaflammation via the Hippo-YAP/TAZ-ROS signaling axis during obesity 3. Similarly, in cardiac endothelial cells under hyperglycemic stress, SELENOM overexpression decreases ROS levels and preserves tight junction proteins through enhanced Parkin-mediated mitophagy, protecting against diabetic cardiovascular complications 4. In cancer biology, SELENOM modulates endoplasmic reticulum (ER) stress and apoptosis; its knockdown increases pro-apoptotic gene expression (CHOP, PUMA, BIM) in glioblastoma cells 5, while recombinant SELENOM induces dose-dependent cytotoxicity through ER stress and IRE1α pathway activation 6. These findings indicate SELENOM's potential therapeutic value in metabolic disease, diabetes-related complications, and cancer treatment.