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Dysregulation of these phase states acts as a pathogenic driver of diverse intractable diseases, including neurodegeneration, cancer, and autoimmune disorders. The intrinsic properties of biomolecular condensates, self\u2010assembly, dynamic reversibility, and environmental responsiveness, also offer a robust blueprint for next\u2010generation biomaterial design. Despite rapid progress across the field, a cohesive framework linking phase transition physics, pathological mechanisms, and translational engineering remains absent. Here, we delineate the full continuum of liquid\u2010liquid, liquid\u2010gel and liquid\u2010solid phase separation, elucidating how dynamic interconversion across phase states regulates core physiological processes and drives the pathogenesis of neurodegeneration, cancer and autoimmune disorders. Meanwhile, we establish a property\u2010design\u2010function paradigm that translates the physicochemical rules of phase separation into rational biomaterial engineering. Building on this mechanistic foundation, we systematically evaluate emerging therapeutic strategies that target aberrant condensates via either BPS induction or inhibition. We also highlight BPS\u2010inspired biomaterials across cell\u2010mimetic systems, responsive drug delivery platforms, bioactive scaffolds, and high\u2010performance imaging probes. Key translational challenges and forward\u2010looking pathways are discussed alongside these advances. This review provides an integrated cross\u2010disciplinary perspective bridging physicochemical fundamentals, pathological implications, and biomedical engineering.<\/jats:p>","DOI":"10.1002\/advs.78087","type":"journal-article","created":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T03:28:29Z","timestamp":1791516509000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Decoding Biomolecular Phase Separation: From Physiological Roles to Pathological Mechanisms and Therapeutic Biomaterials Design"],"prefix":"10.1002","author":[{"given":"Jiawei","family":"Zhu","sequence":"first","affiliation":[{"name":"College of Laboratory Medicine and Life sciences Cixi Institute of Cancer Research Cixi People's Hospital Wenzhou Medical University  Ningbo Zhejiang China"},{"name":"Cixi Biomedical Research Institute Wenzhou Medical University  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingbo","family":"Dong","sequence":"additional","affiliation":[{"name":"College of Laboratory Medicine and Life sciences Cixi Institute of Cancer Research Cixi People's Hospital Wenzhou Medical University  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiufang","family":"Gong","sequence":"additional","affiliation":[{"name":"College of Laboratory Medicine and Life sciences Cixi Institute of Cancer Research Cixi People's Hospital Wenzhou Medical University  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5833-7381","authenticated-orcid":false,"given":"Xuejiao","family":"Song","sequence":"additional","affiliation":[{"name":"School of Physical and Mathematical Sciences Nanjing Tech University (NanjingTech)  Nanjing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhifa","family":"Shen","sequence":"additional","affiliation":[{"name":"College of Laboratory Medicine and Life sciences Cixi Institute of Cancer Research Cixi People's Hospital Wenzhou Medical University  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao","family":"Liang","sequence":"additional","affiliation":[{"name":"College of Laboratory Medicine and Life sciences Cixi Institute of Cancer Research Cixi People's Hospital Wenzhou Medical University  Ningbo Zhejiang China"},{"name":"Cixi Biomedical Research Institute Wenzhou Medical University  Ningbo Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,8]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1038\/s41573-022-00505-4","article-title":"Modulating Biomolecular Condensates: A Novel Approach to Drug Discovery","volume":"21","author":"Mitrea D. 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