Alterations of purinergic signals have been associated with major CNS disorders including chronic pain, brain trauma, ischemia, epilepsy, multiple sclerosis (MS) as well as neurodegenerative diseases, such as Alzheimer disease (AD) or ALS [11–14, 28–33] with a pivotal role for P2X4 receptors (P2X4) [23–25, 34–38]. The gene discussed is P2RX4; the disease is amyotrophic lateral sclerosis.