Barrier-to-Autointegration Factor 1: a key regulator of nuclear envelope integrity, genome stability, and disease...

Barrier-to-Autointegration Factor 1 (BANF1) is a self-associating protein encoded within the q13.1 locus of chromosome 11. It is integral to multiple cellular processes, including cell cycle regulation, chromatin organization, gene expression modulation, nuclear envelope (NE) repair, DNA damage repair (DDR), innate immune function, and viral infection control. While prior investigations have provided preliminary phenotypic and bioinformatic characterizations of BANF1 across various disease states, comprehensive analyses detailing its functional roles and mechanistic underpinnings in diverse pathological contexts remain scarce. In cancer, BANF1 is frequently upregulated, with cancer cells leveraging its functions to preserve NE integrity, inhibit activation of the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) immune pathway, and facilitate epithelial-mesenchymal transition (EMT). These activities contribute to enhanced genomic stability and promote tumor cell proliferation and migration, thereby conferring oncogenic properties. In neurodegenerative diseases, BANF1 is implicated in disease pathogenesis, exemplified by its mediation of glutamate-induced oxidative stress and apoptosis in neuronal cells, as observed in Alzheimer's disease (AD). Additionally, rare mutations in BANF1 are associated with hereditary conditions: the recessive Ala12Thr (A12T) variant causes Néstor-Guillermo progeria syndrome (NGPS), whereas the dominant Gly16Arg (G16R) mutation results in dominant motor neuronopathy. This review further synthesizes recent progress in exploring BANF1 as a therapeutic target, encompassing the development of small-molecule inhibitors, immunomodulatory approaches, and its potential applications in cancer treatment. Overall, this article provides a comprehensive overview of BANF1's structural features, cellular functions, and involvement in disease initiation and progression, with particular emphasis on its expression profiles in malignancies and the therapeutic promise of BANF1-directed interventions.