The endoplasmic reticulum consists of peripheral tubular networks connected to sheet-like domains surrounding the nucleus. Gerondopoulos et al. reveal that the Rab3GAP complex, which is mutated in the neurodevelopmental disorder Warburg Micro Syndrome, is a guanine nucleotide exchange factor that activates the small GTPase Rab18 (also mutated in Warburg Micro Syndrome) to control the balance between ER tubules and sheets.
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