Endosomal trafficking has been implicated as a common molecular pathway disrupted in several neurodevelopment disorders such as Autism Spectrum Disorders (ASDs), schizophrenia (SZ), and Rett Syndrome (RTT). Endosomal trafficking regulates the transport of vesicles from the donor membrane to the acceptor membrane within the endosomal organelles including the Golgi, the early endosome, the recycling endosome, and the lysosome. Trafficking within the endosomal pathway is regulated at the organelle by GTPases as well as their activating proteins, coat proteins like Adaptor Protein 3 (AP3), and the biogenesis of lysosome related organelles complex 1 (BLOC-1), as well as SNARE complexes that are specific for that organelle. Within a neuron, endosomal trafficking is necessary for proper dendritic spine outgrowth, synaptic formation, and the recycling of receptors. Neurodevelopmental disorders alter emotion, cognition, communication, and learning due to aberrant development of the central nervous system. RTT is a neurodevelopmental disorder characterized by impairments in speech, learning and memory, sensory processing, movement, loss of effective hand use, social anxiety, sleep disturbances, and seizures. Because of shared phenotypes, RTT was previously categorized as an ASD (DSM IV). Physical and occupational therapy can improve movement, balance and purposeful hand use, and language therapy can assist with nonverbal communication. Medications can manage some symptoms of RTT including breathing, sleep, GI, and cardiac problems. However, a gap remains in our ability to greatly improve the quality of life for patients with RTT due to insufficient understanding of how RTT alters brain function during development.