Synaptic malformation and dysfunction are highly associated with various neurological disorders, including both neurodevelopmental disorders and neurodegenerative diseases. In terms of neurodevelopmental disorders, a broad spectrum of diseases have been linked to defective synapses, including mental retardation, autism spectrum disorders (ASD), attention- deficit hyperactivity disorder, and schizophrenia. Both environmental and genetic factors contribute to neurodevelopmental disorders. To uncover the genetic factors of these neurodevelopmental disorders, efforts have been made to identify their disease causative genes. Among these various disorders, genetic studies of ASD have accomplished the most significant achievements. A series of studies using whole-exome and whole-genome sequencing of autism patients has identified ~1000 genetic risk factors of ASD, summarized in the Simons Foundation Autism Research Initiative (https://gene.sfari.org/database/ human-gene/). In addition, comorbidity is common in neurodevelopmental disorders. A specific gene may be involved in multiple neurodevelopmental disorders. So complex pathways and crosstalk are common. Understanding the physiological functions of disease causative genes is necessary to investigate the molecular etiology of such disorders. Based on whole-exome sequencing of patient genomes, synaptic proteins controlling synapse formation and signaling, and nuclear proteins regulating transcriptional regulation have been identified as two major groups of genes contributing to ASD. Arising from studies of Fragile X mental retardation, it is well known that translational regulation is also critical for neuronal function and neurodevelopmental disorders. In this Special Issue, a series of articles has been compiled that report on the recent explosive progress regarding molecular and physiological functions of neurodevelopmental disorder-causative genes and the long-lasting effects of psychostimulant, one of environmental factors, on neuronal response (Figure 1). The relevance to circuit defects and disease mechanisms is also discussed. Some highlights of these articles are described below.