The cerebral cortex is one of the most evolutionarily complex structures of the central nervous system (CNS), requiring tightly coordinated steps such as neuronal differentiation and migration from progenitor zones in the ventricular area to the cortical plate. Small GTPases play key roles in these processes by regulating intracellular trafficking, cytoskeleton dynamics, and the transport of adhesion molecules and membrane receptors essential for neurodevelopment. Rab35, a GTPase involved in endosomal and exosomal trafficking, has been identified as an important regulator of neurite growth. This project aims to investigate the role of Rab35 in neuronal differentiation and migration, and its implications in Down syndrome (DS), a condition characterized by altered neurodevelopment and defects in endo/exosomal pathways. Specifically, we will examine whether Rab35 regulates the trafficking and recycling of neurodevelopmental proteins such as the amyloid precursor protein (APP), which may be affected in DS. To address this, we will use primary mouse neurons, DS-iPSC-derived neuronal cultures, and an integrated model combining in utero electroporation (IUE), organotypic cultures, and in situ analyses with super-resolution microscopy.