Protein folding in the endoplasmic reticulum (ER) must couple protein-synthesis pathways operating outside of the compartment with ER-assisted folding (ERAF) pathways in the lumen.

Pathology (Anomalies of protein folding or protein misfolding or protein misfolding diseases)

Chaperone-mediated folding imbalances that are associated with numerous misfolding diseases, including diabetes, trigger the unfolded-protein response (UPR), using both transcriptional and translational pathways to correct the problem.

 diabetes
 amyloidosis
 fibrillin-1 mutations and Marfan disease (#12651868#)

References

 Wiseman RL, Balch WE. A new pharmacology - drugging stressed folding pathways. Trends Mol Med. 2005 Aug;11(8):347-50. PMID: #16005683#

 Ma Y, Hendershot LM. The role of the unfolded protein response in tumour development: friend or foe? Nat Rev Cancer. 2004 Dec;4(12):966-77. PMID: #15573118#

 Daggett V, Fersht A. The present view of the mechanism of protein folding. Nat Rev Mol Cell Biol. 2003 Jun;4(6):497-502. PMID: #12778129#

 Ursini F, Davies KJ, Maiorino M, Parasassi T, Sevanian A. Atherosclerosis: another protein misfolding disease? Trends Mol Med. 2002 Aug;8(8):370-4. PMID: #12127722#

 Horwich A: Protein aggregation in disease: a role for folding intermediates forming specific multimeric interactions. J Clin Invest 110:1221, 2002.

 Hartl FU, Hayer-Hartl M: Molecular chaperones in the cytosol: from nascent chain to folded protein. Science 295:1852, 2002.