Because of the significant involvement of the GDNF at the NMJ, we highlight here the GDNF/NMJ cross-talk in the context of severe disorders such as Alzheimer’s disease (AD), Amyotrophic Lateral Sclerosis (ALS) and Spinal Muscular Atrophy (SMA). The gene discussed is GDNF; the disease is proximal spinal muscular atrophy.