COX2 (mitochondrially encoded cytochrome c oxidase II) is a critical component of mitochondrial complex IV that catalyzes the final step of the electron transport chain, reducing oxygen to water during oxidative phosphorylation. As part of cytochrome c oxidase, COX2 contains the dinuclear copper A center that transfers electrons from cytochrome c to the active site for oxygen reduction [UniProt]. Beyond its essential respiratory function, COX2 plays significant roles in cellular senescence and disease pathogenesis. COX2 methylation and downregulation serve as biomarkers of aging in heart mesenchymal stem cells, where increased methylation correlates with cellular senescence 1. In cancer contexts, COX2 upregulation mediates immune evasion and therapy resistance, particularly in KRAS-mutant lung cancer where it promotes immunotherapy resistance through prostaglandin E2 signaling 2. COX2 also facilitates cancer cell invasion in ovarian cancer through EGF-induced pathways 3. In metabolic syndrome-associated osteoarthritis, senescent preosteoclasts activate COX2-PGE2 signaling, contributing to disease progression 4. Additionally, COX2 participates in reproductive processes, being essential for endometrial decidualization through the COX2/mPGES1/PGE2 pathway 5. Mutations in mitochondrial COX2 cause complex IV deficiency, highlighting its fundamental importance in cellular respiration.