ARF3 is a small GTPase that functions as a central regulator of membrane trafficking and Golgi dynamics. Mechanistically, ARF3 localizes to the trans-Golgi network (TGN) and recycling endosomes 1, where it regulates cargo sorting, vesicle assembly, and controls the integrity of recycling endosomes through interaction with adaptor proteins like GGA1 1. ARF3 also localizes to segregated nanodomains on the TGN and TGN-derived post-Golgi tubules, suggesting distinct roles in post-Golgi sorting 2. Beyond trafficking, ARF3 regulates N-cadherin turnover to control invasion modality and metastasis in cancer 3, and modulates cell proliferation and apoptosis through AKT and ERK pathways 45. Pathogenic ARF3 variants cause neurodevelopmental disorders characterized by developmental delay, epilepsy, and brain abnormalities 16. These variants impair Golgi morphology and trafficking through either loss-of-function or gain-of-function mechanisms, disrupting neural precursor proliferation and cell polarity-dependent movements 6. ARF3 variants have also been identified in idiopathic speech delay 7. Clinically, ARF3 expression serves as a prognostic biomarker in gastric cancer and acute myeloid leukemia, with reduced ARF3 correlating with worse outcomes and potential therapeutic targeting implications 45.