INO80E (INO80 complex subunit E) encodes a putative regulatory component of the chr16-remodeling INO80 complex involved in transcriptional regulation, DNA replication, and DNA repair. As a member of the INO80 complex, INO80E participates in chr16 remodeling and regulation of chromosome 16, cell cycle progression, and DNA strand elongation 1. Mechanistically, INO80E expression is regulated through sense/antisense interactions with its head-to-head overlapping partner HIRIP3, where overlapping transcripts form RNA:RNA duplexes that stabilize mRNAs, potentially mediated by ELAVL1 protein, while R-loops may also positively regulate gene expression 2. INO80E has emerged as a significant risk gene across multiple neurodevelopmental and neurological disorders. Elevated INO80E mRNA expression in the frontal cortex associates with schizophrenia risk 3, and mice overexpressing Ino80e in the medial prefrontal cortex exhibit schizophrenia-like behaviors including anxiety, anhedonia, and impaired prepulse inhibition, with altered dendritic spine density and dysregulated synaptic gene expression 3. INO80E dysregulation in excitatory neurons' superficial cortical layers is influenced by schizophrenia polygenic risk 1. Additionally, INO80E has been identified as a genetic risk factor for Lewy body dementia 4, shared genetic architecture with obesity and psychiatric disorders 5, and as a potential diagnostic marker for endometriosis 6. These findings position INO80E as a pleiotropic gene with favorable neuropsychiatric profiles 7.