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Protein S\u2010glutathionylation (PSSG) is a reversible redox modification that protects cysteines from irreversible oxidation and regulates protein function. Here, we report stage\u2010 and tissue\u2010dependent defects in PSSG levels, accompanied by tissue\u2010specific alterations in the expression of glutathione\u2010related enzymes in Taiwanese SMA mice at early and late symptomatic stages. Importantly, we also provide evidence linking glutathione homeostasis defects with ferroptosis. Finally, partial restoration of SMN by antisense oligonucleotides selectively modulates these abnormalities in a tissue\u2010dependent manner. Our findings suggest S\u2010glutathionylation dysregulation as a novel SMA hallmark and highlight persistent redox imbalance as a therapeutic target beyond SMN restoration.<\/jats:p>\n                  <jats:p>\n                    <jats:boxed-text content-type=\"box\" position=\"anchor\">\n                      <jats:caption>\n                        <jats:title>Impact statement<\/jats:title>\n                      <\/jats:caption>\n                      <jats:p>This study provides a multi\u2010organ analysis of redox imbalance in spinal muscular atrophy, revealing systemic loss of protein S\u2010glutathionylation in a stage\u2010 and tissue\u2010dependent manner. By identifying the heart as particularly redox\u2010vulnerable, this work refines understanding of oxidative stress beyond motor neurons and informs tissue\u2010aware therapeutic evaluation.<\/jats:p>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1002\/1873-3468.70303","type":"journal-article","created":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T08:53:26Z","timestamp":1770972806000},"page":"2262-2282","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Organ\u2010specific redox imbalances in spinal muscular atrophy mice are partially rescued by\n                    <scp>SMN<\/scp>\n                    antisense oligonucleotides"],"prefix":"10.1002","volume":"600","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5816-8269","authenticated-orcid":false,"given":"Sofia","family":"Vrettou","sequence":"first","affiliation":[{"name":"Institute of Human Genetics University Hospital 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