RABGAP1 is a RAB GTPase-activating protein that regulates intracellular trafficking through modulation of RAB GTPase activity. Mechanistically, RABGAP1 controls endosomal positioning and vesicular trafficking by modulating Rab-regulated processes, with its GAP activity directly influencing compartment localization 1. A novel and clinically significant function emerged recently: RABGAP1 acts as a sensor for amyloid precursor protein (APP) trafficking by directly binding the YENPTY motif in APP's cytosolic tail, thereby regulating APP sorting and proteolytic processing 2. This trafficking function affects amyloid-β generation, implicating RABGAP1 in Alzheimer's disease pathogenesis. Biallelic loss-of-function RABGAP1 variants cause a novel neurodevelopmental syndrome characterized by global developmental delay, microcephaly, sensorineural hearing loss, seizures, and white matter abnormalities 3. Functionally, RABGAP1 loss impairs mTOR signaling and causes abnormal early endosome and lysosome localization. RABGAP1 shows pleiotropic associations with metabolic traits including type 2 diabetes and obesity 4, and genome-wide association studies link RABGAP1 variants to cortical structural phenotypes and birth weight 5. These findings position RABGAP1 as a critical regulator of vesicular trafficking with disease relevance spanning neurodegeneration, neurodevelopmental disorders, and metabolic disease.