Abstract: Gαo is the major G protein in neurons, where it transduces signals from numerous G protein-coupled receptors (GPCRs) such as D2 dopamine, μ-opioid, M2 muscarinic, or α2-adrenergic receptors. In 2013, the first mutations in GNAO1, the gene encoding Gαo, were described in pediatric patients with encephalopathies (Nakamura et al., 2013), suffering from movement disorders, epileptic seizures, and developmental delay. As of today, over 200 patients have been identified as GNAO1 mutation carriers (https://gnao1.org/) mainly thanks to the availability of the whole exome sequencing technique. The mutations are typically single amino acid substitutions that mostly occur de novo, however unique cases of inheritance of the mutations are reported as well. In the OMIM (Online Mendelian Inheritance in Man) catalog, the two following disorders are associated with the heterozygous mutation in GNAO1 (the homozygous mutations have never been detected in humans; thus, it is likely that mutations in both alleles are lethal):