Although later mutational screening in worldwide ALS populations established that PFN1 gene mutations are a very rare cause of familial ALS (van Blitterswijk et al., 2013), these findings, together with the association of familial ALS to rare mutation in cytoskeleton-regulating genes such as neurofilament heavy polypeptide, peripherin and dynactin provide a considerable genetic basis to disruption of actin cytoskeleton as a possible pathogenic mechanism in motor neuron degeneration (Renton et al., 2014). This evidence concerns the gene NEFH and amyotrophic lateral sclerosis.