Defects in axonal transport and cytoskeleton in ALS patients are recognizable by the swelling of the axon’s initial segment (AIS) on MNs (i.e., the region of action potential initiation), within which lysosomes, vesicles, mitochondria, and IFs, including Nfls, accrue [72]. Here, SPRED1 is linked to amyotrophic lateral sclerosis.