Defects in the secretory pathway are also linked to ALS. Depletion of TDP-43 inhibits endosomal trafficking and results in lack of neurotrophic signaling and neurodegeneration (Schwenk et al., 2016). Similarly, inhibition of the first part of the classical secretory pathway, ER-Golgi transport, is also induced by mutant SOD1, TDP-43 and FUS (Sundaramoorthy et al., 2013; Soo et al., 2015). This mechanism has been described as a possible trigger for ER stress (Soo et al., 2015), which, as detailed above, is linked to neuronal susceptibility. Both endosomal and ER-Golgi transport are also linked to transport within the axon. However, it remains to be determined if these other forms of trafficking are directly associated with selective neuronal susceptibility in ALS.