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The Golgi Associated RAB2 Interactors (GARINs; also known as FAM71) protein family shows predominant expression in the testis and all possess a RAB2-binding domain which confers binding affinity to RAB2, a small GTPase that is responsible for membrane transport and vesicle trafficking. Our previous study showed that GARIN1A and GARIN1B are important for acrosome biogenesis and that GARIN1B is indispensable for male fertility in mice. Here, we generated KO mice of other <jats:italic>Garins<\/jats:italic>, namely <jats:italic>Garin2<\/jats:italic>, <jats:italic>Garin3<\/jats:italic>, <jats:italic>Garin4<\/jats:italic>, <jats:italic>Garin5a<\/jats:italic>, and <jats:italic>Garin5b<\/jats:italic> (<jats:italic>Garin2-5b<\/jats:italic>). Using computer-assisted morphological analysis, we found that the loss of each <jats:italic>Garin2-5b<\/jats:italic> resulted in aberrant sperm head morphogenesis. While the fertilities of <jats:italic>Garin2<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> and <jats:italic>Garin4<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> males are normal, <jats:italic>Garin5a<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> and <jats:italic>Garin5b<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> males are subfertile, and <jats:italic>Garin3<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> males are infertile. Further analysis revealed that <jats:italic>Garin3<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> males exhibited abnormal acrosomal morphology, but not as severely as <jats:italic>Garin1b<\/jats:italic><jats:sup><jats:italic>-\/-<\/jats:italic><\/jats:sup> males; instead, the amounts of membrane proteins, particularly ADAM family proteins, decreased in <jats:italic>Garin3<\/jats:italic> KO spermatozoa. Moreover, only <jats:italic>Garin4<\/jats:italic> KO mice exhibit vacuoles in the sperm head. These results indicate that GARINs assure correct head morphogenesis and some members of the GARIN family function distinctively in male fertility.<\/jats:p>","DOI":"10.1371\/journal.pgen.1011337","type":"journal-article","created":{"date-parts":[[2024,6,27]],"date-time":"2024-06-27T21:08:27Z","timestamp":1719522507000},"page":"e1011337","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":15,"title":["Golgi associated RAB2 interactor protein family contributes to murine male fertility to various extents by assuring correct morphogenesis of sperm heads"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-5176-7170","authenticated-orcid":true,"given":"Haoting","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0104-1974","authenticated-orcid":true,"given":"Rie","family":"Iida-Norita","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3927-3076","authenticated-orcid":true,"given":"Daisuke","family":"Mashiko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anh Hoang","family":"Pham","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4758-5803","authenticated-orcid":true,"given":"Haruhiko","family":"Miyata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9859-6217","authenticated-orcid":true,"given":"Masahito","family":"Ikawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,6,27]]},"reference":[{"key":"pgen.1011337.ref001","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1242\/dev.02752","article-title":"Sperm binding to the zona pellucida is not sufficient to induce acrosome exocytosis","volume":"134","author":"B Baibakov","year":"2007","journal-title":"Development"},{"key":"pgen.1011337.ref002","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1093\/biolre\/ioy045","article-title":"Sperm acrosome reaction: its site and role in fertilization","volume":"99","author":"N Hirohashi","year":"2018","journal-title":"Biol Reprod"},{"key":"pgen.1011337.ref003","doi-asserted-by":"crossref","DOI":"10.1126\/sciadv.ade7607","article-title":"Testis-enriched ferlin, FER1L5, is required for Ca2+activated acrosome reaction and male fertility","volume":"9","author":"A Morohoshi","year":"2023","journal-title":"Sci Adv"},{"key":"pgen.1011337.ref004","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1093\/humupd\/1.1.51","article-title":"The human sperm acrosome reaction: physiology and regulatory mechanisms. 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