Over the years, studies on various disease mechanisms including endoplasmic reticulum (ER) stress, oxidative stress, excitotoxicity, inhibition of the proteasome, mitochondrial damage, dysregulation of RNA metabolism, axonal disorganization and disrupted axonal transport have been implicated in SOD1- and TDP43-ALS [5,6,7,8,9,10]. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.