SOD3 (superoxide dismutase 3) is an extracellular copper and zinc-containing enzyme that catalyzes the dismutation of superoxide anions to hydrogen peroxide and oxygen, serving as a critical antioxidant defense system in extracellular spaces 1. Unlike the intracellular SOD1 and mitochondrial SOD2, SOD3 exists as a tetramer with a signal peptide that directs it exclusively to extracellular compartments 1. The enzyme functions by converting toxic superoxide radicals, thereby protecting tissues from oxidative damage and maintaining redox balance 2. SOD3 plays important roles in cardiovascular health by preventing oxidative inactivation of nitric oxide and reducing peroxynitrite formation 2. Recent research reveals SOD3's involvement in metabolic regulation, where maternal exercise increases placental SOD3 expression, leading to improved offspring glucose tolerance through epigenetic modifications 3. In joint health, SOD3 protects cartilage extracellular matrix from oxidative damage, and its deficiency accelerates osteoarthritis progression 4. Additionally, SOD3 regulates bone metabolism by promoting osteogenesis and inhibiting adipogenesis through PI3K/AKT and MAPK pathways 5. Clinical significance includes associations between SOD3 polymorphisms and oral health quality of life 6, while therapeutic applications involve SOD3-enriched exosomes for osteoarthritis treatment 7.