Introduction

The endoplasmic reticulum (ER) serves as the primary cellular protein processing factory where polypeptides destined for secretion or membrane insertion are folded. This membrane-bound organelle recruits translating ribosomes, translocates newly synthesized peptides into its lumen, and promotes a variety of post-translational modifications and chaperone-facilitated folding events. Additionally, in higher eukaryotes ER serves as the major intracellular Ca2+ store. Because the ER encompasses about half the total membrane area and one-third the newly translated proteins in a typical eukaryotic cell, its proper function is critical for numerous aspects of cell physiology, including vesicle trafficking, lipid and membrane biogenesis, and protein targeting and secretion. Accordingly, metazoan cells react rapidly to ER dysfunction through a set of adaptive pathways known collectively as the ER stress response (ESR).