Targeting and translocation of proteins to the endoplasmic reticulum at a glance.

The evolutionary emergence of organelles was a defining process in diversifying biochemical reactions within the cell and enabling multicellularity. However, compartmentalization also imposed a great challenge-the need to import proteins synthesized in the cytosol into their respective sites of function. For example, one-third of all genes encode for proteins that must be targeted and translocated into the endoplasmic reticulum (ER), which serves as the entry site to the majority of endomembrane compartments. Decades of research have set down the fundamental principles of how proteins get from the cytosol into the ER, and recent studies have brought forward new pathways and additional regulators enabling better definition of the rules governing substrate recognition. In this Cell Science at a Glance article and the accompanying poster, we give an overview of our current understanding of the multifaceted and regulated processes of protein targeting and translocation to the ER.