SELENOF (selenoprotein F) is a selenium-containing protein localized to the endoplasmic reticulum lumen that functions as a redox enzyme involved in protein quality control. SELENOF belongs to a thioredoxin-like protein family 1 and contains selenocysteine, the biological form of selenium 1. Mechanistically, SELENOF participates in disulfide bond formation and protein folding regulation by enhancing the catalytic activity of UGGT1 and UGGT2, which serve as glycoprotein folding sensors 2. SELENOF binds specifically to the TRXL2 domain of UGGT1, positioning itself to assess misfolded glycoproteins 2. Beyond protein folding, SELENOF regulates glucose and lipid metabolism by modulating mitochondrial oxidative phosphorylation and ATP synthesis, partly through adenosine monophosphate kinase activation 3. SELENOF knockout in young mice causes glucose metabolism disorders including hyperglycemia and impaired insulin sensitivity through disrupted redox homeostasis 4. Clinically, SELENOF acts as a tumor suppressor: loss of SELENOF expression correlates with breast and prostate cancer development and poor patient outcomes 56, while restoration enhances therapeutic response 5. Notably, SELENOF loss may be protective against colon cancer 1. SELENOF polymorphisms associate with increased cancer risk, with disparities in African Americans linked to lower selenium levels and reduced SELENOF expression 6.