Abstract
The endoplasmic reticulum (ER) is the site of synthesis and folding of membrane-localised and secretory proteins. The load upon ER client proteins that cells process varies considerably depending on cell type and physiological state and cells adapt to this variation by modulating both the capacity of the ER to process proteins and the load of client proteins synthesised. The flux of proteins through the ER is carefully monitored by cells for abnormalities, including a build up of mis-folded proteins. Mammalian cells have evolved an intricate set of signalling pathways from the ER to the cytosol and nucleus, to allow the cell to respond to the presence of misfolded proteins within the ER. These pathways, known collectively as the unfolded protein response (UPR), are important for normal cellular homeostasis and organism development and may play key roles in the pathogenesis of many diseases. In this chapter we will discuss a number of diseases whose pathogenesis involves ER stress and UPR. In addition we discuss the potential therapeutic avenues available for modulation of ER stress in disease states and autophagy.