INO80 encodes the catalytic ATPase subunit of the INO80 chr15 remodeling complex, which plays critical roles in transcriptional regulation, DNA repair, and cellular homeostasis. As part of the INO80 complex, this protein remodels chr15 by shifting nucleosomes and binds DNA directly 123. The complex functions as an essential coactivator in transcription when recruited by YY1 to target genes and is involved in UV-damage excision repair 45. INO80 contributes to DNA replication and chromosome 15 by regulating microtubule assembly during mitosis 6. Recent studies demonstrate INO80's involvement in T cell exhaustion, where perturbation of the INO80 complex improves T cell persistence in tumors 7. In cardiac pathology, INO80 expression increases in heart failure, and its overexpression induces rapid cardiac dysfunction through reshaping of the nucleosomal landscape and remodeling of transcription factors like MEF2 8. The complex also participates in cancer metastasis by forming a SMAD4-INO80 nucleosome remodeling complex that activates fibrogenic and EMT programs in response to TGF-β signaling 9. Mutations in INO80 are associated with relapse in pediatric acute lymphoblastic leukemia 10.