The aging process is characterised by tissue decline and the onset of age-associated diseases. It is not, however, immutable, and can be modulated by manipulating the cell signalling pathways perturbed as cells and organisms age. A key characteristic of aging is the progressive accumulation of damaged/unfolded proteins in the endoplasmic reticulum (ER) leading to activation of the unfolded protein response (UPR). The UPR is the collective name for a number of cell signalling pathways that act in concert to restore normal cellular function by halting protein synthesis, clearing misfolded proteins and increasing the production of molecular chaperones. PERK, an ER-resident protein kinase, is critical to the UPR and acts to stall global protein synthesis. However inappropriate PERK activity is associated with the pathology of several age-related disorders including degenerative neurological diseases and cancer. Despite this key role for PERK very few direct substrates have been identified.