TARDBP and amyotrophic lateral sclerosis: TDP-43, FUS and C9ORF72 have also been linked with the formation of insoluble, cytoplasmic aggregates characteristic of degenerating motor neurons in ALS (Blokhuis et al., 2013) and although the impact of protein aggregates in disease pathology is still being determined, one could see these inclusions as physical barriers preventing transport of vital cargos (mRNA transcripts or protein) to the distal axon, and thus interfere with synaptic function which in turn affects motor neuron health.