License to drive: Receptor-mediated ER exit of proteins and lipids

The secretory pathway, which begins at the endoplasmic reticulum (ER) through the COPII complex, is responsible for transporting proteins and lipid carriers to various destined cellular compartments or extracellular space. The fundamental mechanism by which the COPII operates is evolutionarily conserved. Nevertheless, the vast diversity of mammalian cargos poses significant challenges to the secretory pathway, especially considering the intricate physiology in vivo. Particularly, certain physiologically essential cargos, including procollagen and lipoproteins, appear to be oversized for these canonical carriers, implying the need for additional sophisticated regulation at the onset step so-called ER exit. Emerging evidence highlights the critical role of cargo receptors in selective sorting for ER export, illuminating the complex biology of the trafficking dynamics, which holds broad implications for human health and diseases.