Calnexin family members as modulators of genetic diseases

The endoplasmic reticulum (ER) is an intracellular compartment devoted to t he synthesis, segregation and folding of soluble and membrane secretory pro teins. Some mutations in these proteins lend to their incorrect or incomple te folding in the ER. The ER has a quality cont, ol system which detects mi sfolded proteins and then specifies their fate. Some mutated proteins are r etained in the ER wherein they accumulate (Russell bodies for misfolded imm unoglobulin heavy chains, the PiZZ for alpha 1-antitrypsin), others are ret rotranslocated from the ER and degraded by the cytosolic proteasomal system , and yet other proteins are eventually secreted (in AZC-treated cells). In this review we summarize the role of ER resident proteins in quality contr ol of mutated secretory proteins.