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Here we report that VINE acts through its catalytic GEF domain to positively regulate the Rab5-related GTPase Ypt10 and establish a pool of Ypt10 at late endosomes. Ypt10 activation occurs downstream of Vps21 activity, placing Ypt10 within a late endosomal Rab cascade. Genome-wide protein-protein interaction screens revealed a VINE-dependent proximity interaction between Ypt10 and the GEF Mon1-Ccz1. Our data suggest that VINE and Ypt10 regulate late endosomal recruitment of Mon1-Ccz1 to enhance the activation of its substrate, the Rab7 homolog Ypt7. Together, these findings define a Vps21-VINE-Ypt10 regulatory module that adds a layer of control within the late endosomal Vps21-to-Ypt7 cascade and establishes VINE as a dual Rab regulator. Through opposing activities on Vps21 and Ypt10, VINE may couple Rab5 inactivation to Mon1-Ccz1 recruitment to provide more precise control of degradative protein traffic to the vacuole.<\/jats:p>","DOI":"10.1091\/mbc.e26-07-0303","type":"journal-article","created":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T17:11:36Z","timestamp":1788973896000},"source":"Crossref","is-referenced-by-count":0,"title":["The VPS9-family GEF VINE activates Ypt10 in a late endosomal Rab cascade"],"prefix":"10.1091","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5634-3235","authenticated-orcid":false,"given":"Mia S.","family":"Frier","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, University of British Columbia, Vancouver BC V6H 3N1"},{"name":"Centre for Molecular Medicine and Therapeutics, British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver BC V5Z 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