{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nPHF5A is a small, highly conserved nuclear protein that serves as a critical component of the SF3b spliceosome complex. Structural and mutational studies have revealed that key residues within its PHD‐finger domain—such as Y36—mediate interactions with splicing modulators, thereby influencing branch point recognition and pre-mRNA splicing fidelity. Moreover, its ubiquitous expression and essentiality for cell viability, as demonstrated in model organisms, point to an important chromatin‐associated role in maintaining proper RNA processing."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn diverse cancer types including glioblastoma, breast cancer, lung adenocarcinoma, and colon cancer, deregulation of PHF5A contributes to oncogenic processes through aberrant alternative splicing. In glioblastoma stem cells the protein is required for the accurate recognition of exons with uncommon C‐rich 3′ splice sites, whereas in breast cancer PHF5A maintains spliceosome stability and regulates apoptotic signaling via alternative splicing of targets such as FASTK. Similar oncogenic roles have been observed in lung cancers, where increased PHF5A expression promotes cell proliferation, migration, and resistance to chemotherapeutic agents. Additionally, PHF5A has been implicated in modulating splicing events associated with cancer stem‐like cell phenotypes and even in limiting transgene expression from viruses via its participation in the U2 snRNP complex."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its canonical role in splicing regulation, PHF5A influences additional cellular processes. For instance, it modulates non‐homologous end joining during immunoglobulin class switch recombination by stabilizing histone chaperone complexes, thereby facilitating proper DNA repair. Under cellular stress conditions, post‐translational acetylation of PHF5A further fine-tunes U2 snRNP interactions and alternative splicing programs that promote adaptive gene expression responses. Importantly, rare de novo variants in PHF5A have been linked to developmental disorders, and pan‐cancer analyses highlight its potential as a diagnostic and prognostic biomarker, as well as an immunotherapeutic target. Intriguingly, emerging data also hint at intersections with inflammatory pathways such as NF‐κB signaling in hepatocellular carcinoma, suggesting broader regulatory roles that merit further investigation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Teng Teng, Jennifer Hc Tsai, Xiaoling Puyang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Research progress and therapeutic prospect of PHF5A acting as a new target for malignant tumors."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Zhejiang Da Xue Xue Bao Yi Xue Ban (2022)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.3724/zdxbyxb-2022-0459"}], "href": "https://doi.org/10.3724/zdxbyxb-2022-0459"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36581580"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36581580"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Christopher G Hubert, Robert K Bradley, Yu Ding, et al. 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