Likewise, ALS features progressive upper and lower motor neuron loss, mitochondrial dysfunction and energy deficits, impaired nucleocytoplasmic RNA transport, mislocalization of RNA-binding proteins such as TDP-43, aberrant splicing, and noncoding RNA imbalance [34,35,36,37,38,46,47]. The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.