These models have generated many hypotheses regarding the origin of hyperexcitability in ALS, including imbalance of neurons and interneurons (Clark et al. 2017), and corticomotor mislocalisation of TDP-43 causing hyperexcitability, leading to spinal motor neuron degeneration (Reale et al. 2023). The gene discussed is TARDBP; the disease is amyotrophic lateral sclerosis.