A specific signal sequence directs polypeptides to the ER. While some of these proteins remain as permanent ER residents, others are sorted in the ER lumen before being transferred to their final destination via the secretory pathway. The proteins that enter the ER lumen are called soluble proteins. They undergo appropriate folding, modifications, and quality checks in the ER lumen before being packaged into membrane-enclosed vesicles. These vesicles carry soluble proteins, such as hormones and enzymes, for intracellular distribution to other organelles of the endomembrane system like lysosomes or for secretion into the extracellular environment. Unlike soluble proteins, the integral membrane proteins do not completely translocate into the ER lumen. They simply embed their hydrophobic domains into the ER membrane. The orientation of such transmembrane proteins is secured at the ER membrane and maintained throughout the vesicular transport until they reach their destination, where they form surface receptors or transporters.