The Endoplasmic Reticulum (ER) in eukaryotic cells is a substantial network of interconnected membranes with diverse functions, from calcium storage to biomolecule synthesis. A primary component of the endomembrane system, the ER manufactures phospholipids critical for membrane function throughout the cell. Additionally, the two distinct regions of the ER specialize in the manufacture of specific lipids and proteins.

The rough ER is characterized by the presence of microscopically-visible ribosomes on its surface. As a ribosome begins translation of an mRNA in the cytosol, the presence of a signal sequence directs the ribosome to the surface of the rough ER. A receptor in the membrane of the ER recognizes this sequence and facilitates the entry of the growing polypeptide into the ER lumen through a transmembrane protein complex. With the assistance of chaperones, nascent proteins fold and undergo other functional modifications, including glycosylation, disulfide bond formation, and oligomerization. Properly folded and modified proteins are then packaged into vesicles to be shipped to the Golgi apparatus and other locations in the cell. Chaperones identify improperly folded proteins and facilitate degradation in the cytosol by proteasomes.

Lacking ribosomes, the smooth ER is the cellular location of lipid and steroid synthesis, cellular detoxification, carbohydrate metabolism and storage of calcium ions. Cells that specialize in the secretion of hormones tend to be abundant in smooth ER. Likewise, the detoxifying cells of the liver are rich with smooth ER. Smooth ER is also the cellular storage site of otherwise toxic calcium ions; this stored calcium can then be rapidly released as a signaling molecule, stimulating cellular functions including muscle cell contraction and vesicular release. The storage and rapid reuptake of calcium ions in the ER are facilitated by resident calcium-binding proteins.