Rsad2, also known as viperin, is an interferon-stimulated gene encoding a protein belonging to the radical S-adenosylmethionine (SAM) superfamily of enzymes. It is involved in immunomodulation, mitochondrial metabolism, and exhibits broad-spectrum antiviral activity. It may influence the proliferation and development of immune cells as well as inflammation via different signaling pathways [2,4].

In mouse models, depletion of Rsad2 in pregnant mice exposed to type I interferon inducers significantly reduces lipid accumulation, vascular injury, and embryo development disorders, suggesting its role in pregnancy complications related to excessive type I interferon response in systemic lupus erythematosus (SLE) [1]. In BPA-treated mouse spermatocytes, interfering with Rsad2 expression restores the actin cytoskeleton and intracellular ATP levels, indicating its involvement in BPA-induced male reproductive toxicity [3].

In conclusion, Rsad2 is crucial in multiple biological processes and disease conditions. Its study through gene-knockout mouse models has revealed its significance in pregnancy-related complications in SLE and male reproductive toxicity induced by BPA, providing insights into potential therapeutic targets for these diseases.

References:

1. Ding, Xiaoyu, Zhou, Yonggang, Qiu, Xiaofeng, Fu, Binqing, Wei, Haiming. 2025. RSAD2: A pathogenic interferon-stimulated gene at the maternal-fetal interface of patients with systemic lupus erythematosus. In Cell reports. Medicine, 6, 101974. doi:10.1016/j.xcrm.2025.101974. https://pubmed.ncbi.nlm.nih.gov/39983716/

2. Chen, Siyan, Ye, Jiani, Lin, Yinfang, Gao, Sheng, Hua, Chunyan. 2024. Crucial Roles of RSAD2/viperin in Immunomodulation, Mitochondrial Metabolism and Autoimmune Diseases. In Inflammation, 48, 520-540. doi:10.1007/s10753-024-02076-5. https://pubmed.ncbi.nlm.nih.gov/38909344/

3. Jiang, Xiao, Sun, Shengqi, Shi, Chaofeng, Gu, Jing, Liu, Jinyi. 2024. Rsad2 mediates Bisphenol A-induced actin cytoskeletal disruption in mouse spermatocytes. In Journal of applied toxicology : JAT, 44, 1478-1488. doi:10.1002/jat.4649. https://pubmed.ncbi.nlm.nih.gov/38828519/

4. Honarmand Ebrahimi, Kourosh. . A unifying view of the broad-spectrum antiviral activity of RSAD2 (viperin) based on its radical-SAM chemistry. In Metallomics : integrated biometal science, 10, 539-552. doi:10.1039/C7MT00341B. https://pubmed.ncbi.nlm.nih.gov/29568838/