Arc might also be involved in neuropsychiatric diseases (Table 1). Decreased Arc induction results in anxiety-like and alcohol-drinking behaviors in rats [80]. Fragile X syndrome, the most common inherited cause of mental retardation and autism, results from a decrease in FMRP, which regulates Arc translation [30]. Angelman syndrome, a neurodevelopmental disorder characterized by motor dysfunction and severe mental retardation, is caused by a mutation in UBE3A, which encodes the ubiquitin ligase that targets Arc for degradation [52]. Mutations and copy number variations in UBE3A are also associated with autism spectrum disorders (ASDs) [81]. As discussed above, Arc is involved in synaptic homeostasis, which may be one of the underlying causes of the neuronal dysfunction seen in ASDs [82]. Given these links, a role for Arc in mental retardation and ASDs warrants further investigation. Even in normal aging, Arc expression is disrupted owing to regional changes in Arc methylation [83]. However, it is not always clear whether disruptions in Arc expression are a cause or effect of neuronal dysfunction. Still, the importance of Arc in learning and memory implies that such disruptions result in major behavioral abnormalities even when Arc is not the primary cause of a disease.