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In this study, we identified specific AS events in RAB11FIP3, notably the full\u2010length (RAB11FIP3\u2010FL) isoform and exon 6 exclusion (RAB11FIP3\u2010\u03946). We found that RAB11FIP3 (FL\/\u03946) ratio is significantly elevated in patients with MM and DFUs. Additionally, we demonstrated that knockdown of RAB11FIP3\u2010FL alleviates vascular endothelial damage associated with MM and enhances DFU healing. Furthermore, we identified that HNRNPL promotes the retention of exon 6 in RAB11FIP3\u2010FL, thereby increasing the FL\/\u03946 ratio. Mechanistically, our results show that RAB11FIP3\u2010FL promotes the ubiquitination and degradation of HIF\u20101\u03b1 through NEDD4L, independent of VHL. In conclusion, our study identifies RAB11FIP3\u2010FL as a pathogenic splicing isoform contributing to impaired DFU healing. Knockdown of RAB11FIP3\u2010FL promotes vascular regeneration and accelerates diabetic wound healing, offering new therapeutic targets for DFU treatment.<\/jats:p>","DOI":"10.1111\/jcmm.70663","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T16:39:27Z","timestamp":1754325567000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Disrupted Alternative Splicing of\n                    <scp>RAB11FIP3<\/scp>\n                    Contributes to Diabetic Foot Ulcer Dysfunction"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1341-0268","authenticated-orcid":false,"given":"Dong","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Plastic Surgery Affiliated Hospital of Xuzhou Medical University  Xuzhou China"},{"name":"Xuzhou Medical University  Xuzhou 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