Microexons, a special category of exons, are widely present in the genes of animals and humans. They are highly conserved and usually encode motifs that mediate protein interactions. Their alternative splicing plays a role in regulating protein interaction networks. However, it is still unclear whether there are human-specific microexons and whether they participate in brain disorders. By using exon skipping, the most common alternative splicing event, as an entry point, this study conducted a systematic comparison of eight vertebrate genomes and successfully identified 48 human-specific microexons distributed across 40 genes. Searches of the DECIPHER database revealed that 97.5% (39/40) of the genes containing human-spe-cific microexons had copy number variations linked to intellectual disability phenotypes. An analysis of can-didate genes for brain disorders showed that the 40 genes with human-specific microexons were significantly enriched in schizophrenia candidate genes (18/40). Moreover, the motifs encoded by the 48 microexons me-diated 996 protein interactions through binding to protein domains. The genes encoding these interacting proteins were significantly enriched in candidate genes for schizophrenia, autism spectrum disorder, and in-tellectual disability. Further analysis of transcriptome sequencing data showed that over half of the genes containing human-specific microexons were abnormally expressed in the brain tissues of schizophrenia and autism spectrum disorder patients. These findings collectively suggest that human-specific microexons play critical roles in the human brain and that their mutations may be involved in brain disorders.