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As a key regulator of mRNA 3\u2032\u2010end processing, it participates not only in poly(A) tail synthesis and length regulation but also in alternative polyadenylation (APA). Recent studies have demonstrated that PABPN1 undergoes liquid\u2013liquid phase separation (LLPS) to form dynamic membraneless compartments, such as nuclear speckles and nuclear poly(A) domains (NPADs), and contributes to its physiological functions. Emerging evidence has further implicated PABPN1 in a range of cellular processes. These include downstream consequences of APA dysregulation, such as altered stress responses and cell fate decisions, as well as APA\u2010independent molecular functions, including its direct roles in DNA repair and cell cycle control. Dysregulation of PABPN1 LLPS, driven either by intrinsic expansion of its N\u2010terminal alanine stretch or by altered interactions with regulatory cofactors, promotes a transition from dynamic liquid\u2010like condensates to pathological solid\u2010like aggregates. This phase transition is associated with the pathogenesis of oculopharyngeal muscular dystrophy (OPMD) and contributes to oncogenic APA patterns in various cancers. This review summarizes recent findings on the emerging physiological functions of PABPN1, its phase separation characteristics, and the molecular mechanisms underlying its transition into pathological aggregates.<\/jats:p>","DOI":"10.1002\/wrna.70052","type":"journal-article","created":{"date-parts":[[2026,7,18]],"date-time":"2026-07-18T03:50:01Z","timestamp":1784346601000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Beyond the Poly(A) Tail: The Expanding Functional Landscape of\n                    <scp>PABPN1<\/scp>\n                    and Its Dysregulation in\n                    <scp>OPMD<\/scp>\n                    and Cancer"],"prefix":"10.1002","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3046-0310","authenticated-orcid":false,"given":"Wen\u2010Liang","family":"Guan","sequence":"first","affiliation":[{"name":"Fujian Key Laboratory of Innate Immune Biology, Biomedical Research Center 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