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The adult heart is generally considered a nonregenerative organ. In contrast, the neonatal mammalian heart possesses the unique and transient ability to regenerate after injury. The underlying mechanisms governing heart regeneration remain largely unknown. Previous studies have shown that the nuclear auto\u2010antigenic sperm protein (NASP) plays a crucial role in cell proliferation and tumorigenesis. This study explored the role of NASP in the heart for the first time, emphasizing its effect on cardiac regeneration and repair after injury. NASP exhibited high expression in neonatal myocardium and was observed to increase following apical resection (AR). The influence of NASP on cardiomyocyte proliferation was evaluated by examining cell cycle activity, mitosis, and cytokinesis staining using cardiomyocyte\u2010specific overexpression or knockdown adenovirus 5 vectors. NASP knockdown inhibited heart regeneration in neonatal mice post\u2010AR; whereas, NASP overexpression increased cardiomyocyte proliferation and promoted myocardial repair in adult mice post\u2010MI. Mechanistically, NASP promoted cardiomyocyte proliferation through transcriptionally upregulating platelet\u2010derived growth factor receptor beta (PDGFRB), subsequently activating the downstream AKT\/c\u2010MYC pathway. Our study highlights the key role of NASP in facilitating cardiac regenerative repair after injury, indicating its potential as a novel therapeutic target for MI.<\/jats:p>","DOI":"10.1096\/fj.202501385r","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T11:10:01Z","timestamp":1754910601000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Nuclear Autoantigenic Sperm Protein Promotes Cardiac Regeneration and Repair Through Activating the\n                    <scp>PDGFRB<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    Pathway"],"prefix":"10.1096","volume":"39","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7741-096X","authenticated-orcid":false,"given":"Hao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Cardiology The First Affiliated Hospital With Nanjing Medical University  Nanjing 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