Intellectual disability is present in 30–50% of people with autism spectrum disorder (ASD), suggesting that these disorders might share some genetic variants. Now, Mustafa Salih, Fowzan Alkuraya, Christopher Walsh and colleagues report the identification of loss-of-function alleles of CC2D1A causing multiple combinations of ASD, intellectual disability and seizure disorders in 16 individuals from 4 families (Cell Rep. doi:10.1016/j.celrep.2014.06.039; 24 July 2014). The authors performed linkage analysis on genome-wide SNP data for the three consanguineous families and homozygosity mapping for the one non-consanguineous family, identifying a single region at 19p13 containing CC2D1A that was strongly associated with affected status in all four families. CC2D1A regulates pathways involved in neuronal differentiation, including the NF-κβ signaling pathway. The authors knocked down Cc2d1a in the developing cortex of mice in utero and observed abnormal, underdeveloped dendrites at postnatal day 11. They found that CC2D1A knockdown in neurons led to an increase in NF-κβ target gene transcription and that chemical inhibition of NF-κβ rescued the neuronal CC2D1A knockdown phenotype.