biostudies-literatureDu YNational Key R&D Program of ChinaNational Key R&D Program of ChinaNational Natural Science Foundation of ChinaShenzhen Bay Scholars Programe202402083https://www.ebi.ac.uk/biostudies/studies/S-EPMC11457499biostudies-literatureUnknown223(12)VPS13B/COH1 is the only known causative factor for Cohen syndrome, an early-onset autosomal recessive developmental disorder with intellectual inability, developmental delay, joint hypermobility, myopia, and facial dysmorphism as common features, but the molecular basis of VPS13B/COH1 in pathogenesis remains largely unclear. Here, we identify Sec23 interacting protein (Sec23IP) at the ER exit site (ERES) as a VPS13B adaptor that recruits VPS13B to ERES-Golgi interfaces. VPS13B interacts directly with Sec23IP via the VPS13 adaptor binding domain (VAB), and the interaction promotes the association between ERES and the Golgi. Disease-associated missense mutations of VPS13B-VAB impair the interaction with Sec23IP. Knockout of VPS13B or Sec23IP blocks the formation of tubular ERGIC, an unconvenThe Journal of cell biologySec23IP recruits VPS13B/COH1 to ER exit site-Golgi interface for tubular ERGIC formation.PMC114574992022YFA13028008190116632122025923543043237134332270779Xiong JFan XJi WKSong CDu YDeng LChang WfalseSec23IP recruits VPS13B/COH1 to ER exit site-Golgi interface for tubular ERGIC formation.VPS13B/COH1 is the only known causative factor for Cohen syndrome, an early-onset autosomal recessive developmental disorder with intellectual inability, developmental delay, joint hypermobility, myopia, and facial dysmorphism as common features, but the molecular basis of VPS13B/COH1 in pathogenesis remains largely unclear. Here, we identify Sec23 interacting protein (Sec23IP) at the ER exit site (ERES) as a VPS13B adaptor that recruits VPS13B to ERES-Golgi interfaces. VPS13B interacts directly with Sec23IP via the VPS13 adaptor binding domain (VAB), and the interaction promotes the association between ERES and the Golgi. Disease-associated missense mutations of VPS13B-VAB impair the interaction with Sec23IP. Knockout of VPS13B or Sec23IP blocks the formation of tubular ERGIC, an unconven2024-01-01T00:00:00Z2024 Dec2026-06-02T20:37:43.261Z2026-04-20T03:10:13.632ZS-EPMC114574993935249710.1083/jcb.202402083