Coregulated alternative splicing events involved in developmental and disease processes are largely uncharacterized. Manuel Irimia, Benjamin Blencowe and colleagues developed a computational pipeline to systematically identify all alternative splicing events, including the use of microexons, in RNA sequencing data to better understand which biological processes are affected by specific alternative splicing programs (Cell 159, 1511–1523, 2014). The pipeline was applied to data from over 50 tissue and cell types in human and mouse and was designed to detect microexons—exons less than 27 nt in length—which are often missed in genome annotations. The authors found a group of ∼2,500 neural-regulated splicing events and an enrichment of microexons among neural-specific alternative exons. Moreover, most microexon inclusion events were neural specific and highly conserved between humans and mice. Through analysis of publicly available RNA sequencing data, the authors found that the splicing factor nSR100 (SRRM4) was responsible for the regulation of most alternatively spliced microexons. They experimentally demonstrated that microexon regulation is switched on late during neural differentiation and that microexons likely function to enhance specific protein-protein interactions when spliced in. Finally, the authors found that 30% of alternatively spliced microexons were misregulated in the brains of some individuals with autism spectrum disorder (ASD), and the inclusion of neural-regulated microexons was correlated with nSR100 expression levels across all individuals with ASD analyzed.