Here, we critically review the recent clinical and pre-clinical evidence of the involvement of aberrations in ganglioside metabolism in a range of neuropsychiatric and CNS pathologies, including attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorders (ASD), and review the possible underlying mechanisms, such as neuroinflammation and oxidative stress, insulin signalling dysregulation and myelination abnormalities, as possible pathophysiological patterns resulting from central ganglioside deficiency. Here, INS is linked to attention deficit-hyperactivity disorder.