Alina Guna1, Masami Hazu2, Giovani Pinton Tomaleri2 and Rebecca M. Voorhees2 1Whitehead Institute for Biomedical Research, Massachusetts Institute of Technology, Cambridge, Massachusetts 02142, USA 2Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, California 91125, USA Correspondence: voorheescaltech.edu

Tail-anchored (TA) proteins are an essential class of integral membrane proteins required for many aspects of cellular physiology. TA proteins contain a single carboxy-terminal transmembrane domain that must be post-translationally recognized, guided to, and ultimately inserted into the correct cellular compartment. The majority of TA proteins begin their biogenesis in the endoplasmic reticulum (ER) and utilize two parallel strategies for targeting and insertion: the guided-entry of tail-anchored proteins (GET) and ER-membrane protein complex (EMC) pathways. Here we focus on how these two sets of machinery target, transfer, and insert TAs into the lipid bilayer in close collaboration with quality control machinery. Additionally, we highlight the unifying features of the insertion process as revealed by recent structures of the GET and EMC membrane protein complexes.