My group seeks to understand, in molecular detail, the steps taken by each of the major classes of membrane proteins to achieve their final assembled state. Our recent focus has been on the thousands of human proteins containing more than one transmembrane domain. These multipass membrane proteins function as receptors, channels, enzymes, anchors and transporters, and many human diseases are linked to defects in their biogenesis. In the first part of my talk I will describe our discovery of an endoplasmic reticulum (ER) translocon dedicated to the biogenesis of multipass membrane proteins, and our ongoing efforts to define the molecular basis of its function. A surprising result from this work is that the “multipass translocon” is assembled dynamically in response to features of the nascent chain. In the second part of my talk I will discuss our recent studies to understand more generally how the ER translocon adjusts its subunit composition co-translationally to accommodate the changing biosynthetic needs of its diverse set of clients.