Except for the few proteins that remain permanent residents of the rER membranes and those proteins secreted by the constitutive pathway, the newly synthesized proteins are normally delivered to the Golgi apparatus within minutes. A few diseases are characterized by an inability of the rER to export a mutated protein to Golgi. For example, in 1antitrypsin defciency, a single amino acid substitution renders the rER unable to export 1-antitrypsin (A1AT). This leads to decreased activity of A1AT in the blood and lungs and abnormal deposition of defective A1AT within the rER of liver hepatocytes, resulting in emphysema (chronic obstructive pulmonary disease) and impaired liver function.
In cells in which the constitutive pathway is dominant— namely, plasma cells and activated fibroblasts—newly synthesized proteins may accumulate in the rER cisternae, causing their engorgement and distension.
The rER also serves as a quality checkpoint in the process of protein production. If the newly synthesized protein is not properly post-translationally modified or misfolded, it is then exported from the rER back to the cytoplasm via the mechanism of retrotranslocation. Defective proteins are here deglycosylated, polyubiquitylated, and degraded within proteasomes (see page 44).
The rER is most highly developed in active secretory cells.
The rER is particularly well developed in those cells that synthesize proteins destined to leave the cell (secretory cells) as well as in cells with large amounts of plasma membrane, such as neurons. Secretory cells include glandular cells, activated fibroblasts, plasma cells, odontoblasts, ameloblasts, and osteoblasts. The rER is not limited, however, to secretory cells and neurons. Virtually every cell of the body contains profiles of rER. However, they may be few in number, a reﬂection of the amount of protein secretion, and dispersed so that in the light microscope they are not evident as areas of basophilia.
The rER is most highly developed in active secretory cells because secretory proteins are synthesized exclusively by the ribosomes of the rER. In all cells, however, the ribosomes of the rER also synthesize proteins that are to become permanent components of the lysosomes, Golgi apparatus, rER, or nuclear envelope (these structures are discussed in the next sections) or integral components of the plasma membrane.
Coatomers mediate bidirectional traffic between the rER and Golgi apparatus.
Experimental data indicate that two classes of coated vesicles are involved in the transport of protein from and to the rER. A protein coat similar to clathrin surrounds vesicles transporting proteins between the rER and the Golgi apparatus (page 35). However, unlike clathrins, which mediate bidirectional transport from and to the plasma membrane, one class of proteins is involved only in anterograde transport from the rER to the cis-Golgi network (CGN), the Golgi cisternae closest to the rER. Another class of proteins mediates retrograde transport from the CGN back to the rER (Fig. 2.28). These two classes of proteins are called coatomers or COPs.  COP-I mediates transport vesicles originating in the
CGN back to the rER (Fig. 2.29a). This retrograde proteins mistakenly transferred to the CGN during nor mal anterograde transport. In addition, COP-I is also re the Golgi cisternae.