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Here, we demonstrate that rhomboid intramembrane serine protease Rhbdl2 influences wound repair in zebrafish. We generated rhbdl2 mutants using CRISPR-Cas9 and found that, although Rhbdl2 is dispensable for normal development, its loss triggers enhanced wound repair following injury. This regenerative phenotype is accompanied by increased macrophage migration speed and accumulation at the wound site, as well as elevated early apoptosis and cell proliferation. Proteomic analyses reveal increased Rac2 protein levels in rhbdl2 mutants, which was previously identified as a regulator of leukocyte motility. Functionally, Rac2 morpholino\u2013mediated knockdown in rhbdl2 mutant larvae suppresses the elevated macrophage recruitment and enhanced tissue repair phenotype. Together, these findings identify Rhbdl2 as a modulator of macrophage recruitment to the wound site during tissue repair, with implications for inflammatory disease, fibrosis, and tumor\u2013immune interactions.<\/jats:p>","DOI":"10.1083\/jcb.202602106","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T06:21:18Z","timestamp":1787034078000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Rhomboid protease Rhbdl2 influences macrophage recruitment and wound repair in zebrafish"],"prefix":"10.1083","volume":"225","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9352-0096","authenticated-orcid":true,"given":"Saroj","family":"Gourkanti","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0168r3w48","id-type":"ROR","asserted-by":"publisher"}],"name":"School of Biological Sciences, University of California San Diego 1 Department of Cell and Developmental Biology, , 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