WenJun Zhang School of Life Sciences, Sun Yat-sen University, Guangzhou, China Network Biology ISSN 2220-8879 http://www.iaees.org/publications/journals/nb/online-version.asp 2027 17 1 46 75 International Academy of Ecology and Environmental Sciences Hong Kong 20 April 2026 29 April 2026 1 March 2027 superoxide dismutase oxidative stress antioxidant free radicals SOD mimetics nanozymes therapeutic applications Superoxide dismutase (SOD) constitutes the first line of defense against oxidative stress by catalyzing the dismutation of superoxide anion radicals (O2.-) into molecular oxygen and hydrogen peroxide. Since its discovery in 1969, SOD has been extensively characterized across species ranging from bacteria to mammals, revealing a family of metalloenzymes with distinct metal cofactors, subcellular localizations, and regulatory mechanisms. This comprehensive review synthesizes over five decades of research on SOD, encompassing its discovery history, molecular structure and classification, physicochemical properties, extraction and purification methodologies, pharmacokinetics, and multifaceted pharmacological actions. The therapeutic potential of SOD has been investigated in numerous pathological conditions, including aging, skin photoaging, cardiovascular diseases, neurodegenerative disorders, cancer, radiation injury, diabetic complications, and organ protection. Clinical trials have demonstrated both promise and limitations, with bioavailability remaining a central challenge. Recent advances in SOD mimetics, nanozyme formulations, and targeted delivery systems have opened new avenues for therapeutic application. This review critically evaluates the current state of knowledge, identifies gaps in understanding, and proposes future research directions to harness the full therapeutic potential of SOD. http://www.iaees.org/publications/journals/nb/articles/2027-17(1)/Superoxide-dismutase.pdf