SELENOO (selenoprotein O) is a mitochondrial selenoprotein that catalyzes AMPylation, a posttranslational modification transferring adenosine 5'-monophosphate to serine, threonine, and tyrosine residues on target proteins 1. This enzymatic activity is conserved from bacteria to mammals and essential for oxidative stress response 2. SELENOO functions as a redox-active protein interacting with mitochondrial substrates 3. Mechanistically, SELENOO AMPylates multiple mitochondrial proteins including succinate dehydrogenase subunit A, a key component of mitochondrial complex II, thereby regulating complex II activity and cellular redox homeostasis 2. SELENOO expression is tightly regulated by selenium availability and responds to oxidative stress conditions, with expression altered during heavy metal exposure and selenium deficiency 4, 5. Clinically, SELENOO shows significant disease relevance. In melanoma, high SELENOO expression correlates with metastasis and poor overall survival, while SELENOO deficiency reduces metastatic potential through enhanced mitochondrial complex II activity and increased oxidative stress 2. SELENOO is also downregulated in thyroid cancer and correlates with ER stress, mitochondrial translation, and telomere maintenance 6. Additionally, SELENOO expression is altered in COVID-19 patients and HIV infection contexts, suggesting broader roles in viral pathogenesis and immune regulation 7, 8.