Axonal transport requires the efficient regulation of both dynein and kinesin molecular motors (Melkov et al., 2016), which mediate transport in the retrograde and anterograde directions respectively. Dynein is differentially expressed in vulnerable and susceptible MNs because higher levels are present in spinal and hypoglossal MNs compared to oculomotor neurons (Ilieva et al., 2008). However, dynein levels were significantly decreased in motor nuclei in SOD1G93A mice compared to wild type mice although its expression in MNs was equivalent (Comley et al., 2015). Similar patterns were observed in ALS patients (Comley et al., 2015). Disruption of dynein inhibits axonal transport and results in abnormal redistribution of mitochondria (Varadi et al., 2004) and late-onset degeneration in mice (LaMonte et al., 2002). Several FALS-linked SOD1 mutants co-localize with dynein/dynactin in vitro and SOD1G93A mice (Ligon et al., 2005; Zhang et al., 2007; Shi et al., 2010), which perturbs axonal transport and synaptic mitochondrial content (De Vos et al., 2007). The lower expression of dynein in oculomotor neurons might therefore confer resistance to axonal transport defects in ALS. However, it is also possible that this simply reflects less need for retrograde transport in oculomotor neurons due to their smaller cell bodies, shorter axons and lower requirements for energy, compared to spinal and hypoglossal MNs. Nevertheless, the inefficient axonal transport of mitochondria may confer loss of energy at the synapse in vulnerable MN subpopulations. These MNs require more energy to function than other cells, leading to disturbed synaptic activity.