PACS1 syndrome mutation disrupts dynein-mediated cargo transport via HDAC6 and BICD2

PACS1 syndrome is a neurodevelopmental disorder caused by a recurrent heterozygous missense mutation in PACS1 (p.R203W). Here, we identify cytoplasmic dynein-1 heavy chain (DHC1) as a PACS1 interactor essential for maintaining furin localization at the trans-Golgi network. PACS1R203W induces a dynein loss-of-function phenotype that disrupts furin trafficking and Golgi organization.