It should also be noted, however, that the ER in neurons (and therefore MNs) is not as well characterized as other cell types. In fact, most studies examining UPR mechanisms have involved non-neuronal cells. Neurons possess extensive ER which is distributed continuously throughout the axonal, dendritic and somatic compartments, implying that neurons make unique demands on the ER compared to other cell types (Ramírez and Couve, 2011). Hence, our current soma-centric view of the ER does not consider its role in neuronal processes and how this might relate to their specific functions. This is particularly true for large neurons, such as MNs with their extended axons. The findings that the most susceptible MNs develop ER stress first implies that the ER in MNs may confer unique susceptibility on these cells compared to other MNs and non-neuronal cells. However, this idea requires validation experimentally.