ALS is a multi-system neurodegenerative disorder with both clinical and biological heterogeneity for which the dysregulation of several pathogenic mechanisms related to TDP-43 pathology has been postulated, including disorders of protein homeostasis, RNA processing, nuclear and axonal transport, energy metabolism, dysfunctional immune regulation, oxidative stress, excitotoxicity, endosomal and vesicular transport impairment, autophagy, neuroinflammation involving glial cells and circulating immune cells, and mitochondrial dysfunction [16,23,151,187,188,189,190,191]. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.