Sod2, also known as superoxide dismutase 2, is a mitochondrial protein belonging to the iron/manganese superoxide dismutase family. Its essential function is to convert the superoxide anion, a potentially damaging radical, to the less reactive hydrogen peroxide, thus defending eukaryotic systems against oxidative damage. This process is crucial for maintaining mitochondrial function and overall cellular health. It is involved in multiple biological processes such as cell proliferation, differentiation, and is associated with pathways related to redox homeostasis [3,4].

In SIRT3-related studies, Cd exposure decreased SIRT3 and promoted SOD2 acetylation, reducing SOD2 activity and leading to mitochondrial-derived superoxide anion-dependent autophagic cell death in HepG2 cells, which was ameliorated by SIRT3 overexpression [1]. In osteoblasts, both SOD2 and SIRT3 knockdown suppressed differentiation, and SIRT3-deficient mice showed osteopenia with osteoblast dysfunction, indicating SIRT3/SOD2 is vital for osteoblast differentiation and bone formation [2]. In sickle cell disease, the antioxidant defense system including SOD2 is diminished, and a missense variant in SOD2 is associated with increased sickle complications [6]. Chondrocyte-specific Sod2 deficiency in mice accelerated age-related and mechanical stress-induced disc degeneration [5].

In conclusion, Sod2 plays a central role in maintaining redox homeostasis, especially in mitochondria. Through gene-knockout (KO) or conditional-knockout (CKO) mouse models and other loss-of-function experiments, its significance in various disease conditions such as hepatotoxicity, bone-related disorders, sickle cell disease, and intervertebral disc degeneration has been revealed. These studies help us understand the mechanisms underlying these diseases and may provide potential therapeutic targets.