Brain　size　abnormality　is　correlated　with　an　increased　frequency　of　autism　spectrum　disorder　(ASD)　in　offspring.　Genetic　analysis　indicates　that　heterozygous　mutations　of　the　WD　repeat　domain　62　(WDR62)　are　associated　with　ASD.　However,　biological　evidence　is　still　lacking.　Our　study　showed　that　Wdr62　knockout　(KO)　led　to　reduced　brain　size　with　impaired　learning　and　memory,　as　well　as　ASD-like　behaviors　in　mice.　Interestingly,　Wdr62　Nex-cKO　mice　(depletion　of　WDR62　in　differentiated　neurons)　had　a　largely　normal　brain　size　but　with　aberrant　social　interactions　and　repetitive　behaviors.　WDR62　regulated　dendritic　spinogenesis　and　excitatory　synaptic　transmission　in　cortical　pyramidal　neurons.　Finally,　we　revealed　that　retinoic　acid　gavages　significantly　alleviated　ASD-like　behaviors　in　mice　with　WDR62　haploinsufficiency,　probably　by　complementing　the　expression　of　ASD　and　synapse-related　genes.　Our　findings　provide　a　new　perspective　on　the　relationship　between　the　microcephaly　gene　WDR62　and　ASD　etiology　that　will　benefit　clinical　diagnosis　and　intervention　of　ASD.　©　2022,　The　Author(s).