Having studied the action of adenosine for more than 40 years, using the neuromuscular junction as a model, and considering that this simple synaptic model could be as a sort of key (Arbour et al., 2017) to investigate novel approaches for disease therapy, and also that this particular synapse is compromised in ALS, we hypothesized (Nascimento et al., 2014, 2015) that ALS progression could be accompanied by changes in the functioning of adenosine A1R and A2AR, the two high affinity adenosine receptors known to be expressed at motor nerve endings (Correia-de-Sá and Ribeiro, 1994). The gene discussed is ADORA2A; the disease is amyotrophic lateral sclerosis.