We turn our attention now to the very large class of proteins that are synthesized and sorted in the secretory pathway (see Figure 17-1). Once the ribosomes synthesizing these proteins become bound to the rough ER, the proteins enter or cross the ER membrane cotranslationally — that is, during their synthesis. Soluble proteins in this class first are localized in the ER lumen and subsequently are sorted to the lumen of other organelles or are secreted from the cell. Likewise, the integral membrane proteins in this class initially are inserted into the rough ER membrane during their synthesis; some remain there, but many eventually become localized to the plasma membrane or membranes of the smooth ER, Golgi complex, lysosomes, or endosomes.