Membrane traffic is a highly regulated process that ensures the communication between membrane‐bound compartments while maintaining their specific protein and lipid composition. It can be divided into four steps: cargo sorting and budding of a vesicle from a donor compartment, transport along the cytoskeleton, tethering and docking to an acceptor compartment, and finally fusion with the acceptor compartment. Importantly, defects in any of these steps can lead to diseases that affect different tissues and organs. At the subcellular level, several of these diseases affect compartments from specialized cell types known as lysosome‐related organelles. Moreover, the dysfunction of membrane traffic processes required ubiquitously can lead to restricted phenotypes, underscoring the redundancy of these processes and/or the sensitivity of certain cell types to their impairment. Thus, the study of the diseases caused by defects in membrane traffic provides an opportunity to understand its role in normal cell physiology and discover novel therapies.

Key Concepts:

• Defects in any of the steps of vesicular traffic can lead to disease.

• Vesicular traffic regulation shows redundancy.

• Defects in ubiquitously‐expressed proteins can result in a tissue‐restricted phenotype.

• Lysosome‐related organelles are commonly affected upon impairment of vesicular traffic.

• Several diseases are caused by defects in different proteins involved in the same biological process/pathway.