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Mechanistic studies useful for the study of LCD self-association have evolved over the past decade in the form of simple assays of phase separation. Here, we have used such assays to demonstrate that the interactions responsible for LCD self-association can be dictated by labile protein structures poised close to equilibrium between the folded and unfolded states. Furthermore, missense mutations causing Charcot-Marie-Tooth disease, frontotemporal dementia, and Alzheimer\u2019s disease manifest their pathophysiology in vitro and in cultured cell systems by enhancing the stability of otherwise labile molecular structures formed upon LCD self-association.<\/jats:p>","DOI":"10.1126\/science.abn5582","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T17:59:06Z","timestamp":1656611946000},"source":"Crossref","is-referenced-by-count":108,"title":["Mutations linked to neurological disease enhance self-association of low-complexity protein sequences"],"prefix":"10.1126","volume":"377","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6840-973X","authenticated-orcid":true,"given":"Xiaoming","family":"Zhou","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, TX 75390, 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