BackgroundAutism spectrum disorder (ASD) is a complex neurodevelopment disorder with social and communicational deficiency, language impairment, and ritualistic behaviors. Attention deficit hyperactivity disorder (ADHD) is a pediatric psychiatric disorder with symptoms, including attention deficit, hyperactivity, and impulsiveness. ADHD is a childhood-onset disorder that can persist into adult life. Neuroligins are post-synaptic cell-adhesion molecules that connect neurons and have an essential role in the mediation of trans-synaptic signaling and shaping the synapse and circuits and neural network functioning. AimsPresent study aimed to shed light on the role of the Neuroligin gene family in ASD and ADHD. Methods and proceduresmRNA levels of the Neuroligin gene family (NLGN1, NLGN2, NLGN3, and NLGN4X) were studied in the peripheral blood of 450 unrelated ASD patients, 450 unrelated ADHD patients, and the normal group included 490 unrelated non-psychiatric children by quantitative PCR. Also, clinical situations were considered. Outcomes and resultsResults showed that mRNA levels of NLGN1, NLGN2, and NLGN3 were significantly down-regulated in the ASD group vs. control subjects. In ADHD, a significant reduction of NLGN2 and NLGN3 was detected in comparison with normal children. A comparison of ASD and ADHD subjects revealed that NLGN2 was significantly down-regulated in ASD subjects. ConclusionsThe Neuroligin family gene may play an essential role in the etiology of ASD and ADHD and thus be a source for a better understanding of neurodevelopment disorders. ImplicationsSimilar patterns of deficiency of Neuroligin family genes in ASDs and ADHDs may indicate the role of these genes in functions that have been affected in both disorders.