The article by Simons and van Meer explores the mechanisms of lipid sorting in epithelial cells, focusing on the generation and maintenance of different lipid compositions in the apical and basolateral plasma membrane domains. They highlight the importance of phosphoinositides in signal transduction and the covalent attachment of lipids to proteins, which have gained attention in recent years. The authors discuss the role of the trans-Golgi network in sorting both proteins and lipids into common carrier vesicles for delivery to the correct cell surface domain. They provide detailed insights into the lipid compositions of the apical and basolateral membranes, noting that the apical membrane has a higher glycosphingolipid-to-phospholipid ratio compared to the basolateral membrane. The study also examines the asymmetric distribution of lipids in epithelial plasma membranes, suggesting that tight junctions prevent lipid diffusion between the apical and basolateral domains. The authors propose a model where sphingolipids cluster in the luminal leaflet of the trans-Golgi network, forming a microdomain that interacts with apical proteins to form apical membrane vesicles. They suggest that this process involves specific interactions between glycosphingolipids and proteins, leading to the formation of apical membrane precursor domains. The article concludes by emphasizing the importance of understanding lipid traffic in addition to protein traffic for a comprehensive understanding of intracellular transport.The article by Simons and van Meer explores the mechanisms of lipid sorting in epithelial cells, focusing on the generation and maintenance of different lipid compositions in the apical and basolateral plasma membrane domains. They highlight the importance of phosphoinositides in signal transduction and the covalent attachment of lipids to proteins, which have gained attention in recent years. The authors discuss the role of the trans-Golgi network in sorting both proteins and lipids into common carrier vesicles for delivery to the correct cell surface domain. They provide detailed insights into the lipid compositions of the apical and basolateral membranes, noting that the apical membrane has a higher glycosphingolipid-to-phospholipid ratio compared to the basolateral membrane. The study also examines the asymmetric distribution of lipids in epithelial plasma membranes, suggesting that tight junctions prevent lipid diffusion between the apical and basolateral domains. The authors propose a model where sphingolipids cluster in the luminal leaflet of the trans-Golgi network, forming a microdomain that interacts with apical proteins to form apical membrane vesicles. They suggest that this process involves specific interactions between glycosphingolipids and proteins, leading to the formation of apical membrane precursor domains. The article concludes by emphasizing the importance of understanding lipid traffic in addition to protein traffic for a comprehensive understanding of intracellular transport.