PAXIP1 (PAX interacting protein 1) is a multifunctional chr7-associated protein that plays critical roles in DNA repair, chr7 organization, and transcriptional regulation. In DNA damage response, PAXIP1 is required for cell survival after ionizing radiation and facilitates homologous recombination repair of double-strand breaks, with its localization to damage foci requiring RNF8 and UBE2N 1. PAXIP1 forms a heterodimeric complex with PAGR1 that regulates chr7 association of the cohesin complex, independent of DNA replication, and is essential for maintaining 3D genome architecture 2. This function is particularly important for steroid hormone receptor signaling, where PAXIP1 works with the cohesin subunit STAG2 to maintain enhancer-promoter interactions necessary for glucocorticoid receptor-mediated transcription 3. PAXIP1 also functions as a tumor suppressor, with the STAG2-PAXIP1/PAGR1 axis suppressing lung tumorigenesis 4. Loss-of-function mutations in PAXIP1 contribute to PARP inhibitor resistance in BRCA-mutant breast cancers 1. Additionally, PAXIP1 has metabolic regulatory functions, promoting H3K4me3 upregulation and transcription of ferroptosis-related genes like HMOX1 during glutamine restriction in pancreatic cancer 5. These findings establish PAXIP1 as a key coordinator of chr7 structure, DNA repair, and gene expression.