<p>Membrane trafficking is a fundamental cellular process responsible for transporting proteins and lipids within and between cells, essential for maintaining cellular homeostasis and supporting proper neuronal function. This narrative review examines the role of membrane trafficking in psychiatric disorders, focusing on autism spectrum disorder (ASD) and major depressive disorder (MDD), and discusses its potential as a target for pharmacological interventions. Emerging evidence shows that dysregulation of membrane trafficking is implicated in these conditions. In neurons, this process is central to synaptic transmission, neurotransmitter release, and receptor recycling, supporting neurodevelopment and brain plasticity. Disruptions can lead to altered synaptic connectivity, impaired neuroplasticity, and reduced responsiveness to pharmacological treatments. Recent studies also highlight the involvement of endosomal trafficking pathways, cytoskeletal proteins, and mitochondrial transport in their pathophysiology. Understanding the molecular mechanisms that regulate membrane trafficking may provide new insights into the etiology of ASD and MDD and open avenues for novel therapeutic strategies aimed at improving intracellular communication and neuroplasticity.</p> Graphical Abstract <p>Autism spectrum disorder (ASD) and major depressive disorder (MDD), highlighting proteins and biomolecules involved in membrane trafficking and neuronal communication. In ASD, proteins associated with cytoskeleton dynamics, exocytosis, synaptic formation, and neural plasticity are illustrated, including <i>JAKMIP1</i>, <i>MARK1</i>, <i>Arc/Arg3.1</i>, <i>VAMP2</i>, <i>SNAP25</i>, and <i>NBEA</i>. In MDD, factors related to synaptic plasticity, structural remodeling, and neuronal metabolism are highlighted, such as BDNF-TrkB, serotonin (5-HT), homocysteine, and prions, emphasizing potential targets for research and therapeutic intervention (Created with BioRender.com).</p> <p></p>