Individuals with 2p15p16.1 microdeletion syndrome present with intellectual disability, microcephaly, delayed growth, dysmorphic craniofacial features, and digital abnormalities. The precise genetic region responsible for this syndrome has been challenging to identify. However, recent reports indicate that 4 genes (XPO1, USP34, BCL11A, and REL) are commonly deleted in this syndrome. A study in the current issue of JCI Insight describes 8 new subjects with microdeletions in chromosomal region 2p15p16.1 and provides evidence that loss of XPO1, REL, and BCL11A underlie this syndrome.