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While HOIP-dependent Met1-linked ubiquitination is well established in inflammation and immunity, the physiological importance of its quantitative control remains unclear. Here, we show that cells expressing catalytically inactive HOIL-1 accumulate increased \u03b1-synuclein, tau, and amyloid-\u03b2 aggregates. This is associated with defective late-stage autophagic flux, characterized by impaired delivery of p62-positive aggregates to lysosomes. In parallel, p62 bodies undergo a biophysical transition from dynamic, liquid-like condensates to rigid, solid-like structures. Elevation of Met1-linked ubiquitin chains, either through HOIL-1 inactivation or depletion of the Met1-specific deubiquitinase OTULIN, phenocopies these defects. Together, our findings identify HOIL-1 as a key regulator of aggregate clearance and proteostasis through quantitative control of Met1-linked ubiquitination.<\/jats:p>","DOI":"10.1038\/s44318-026-00909-7","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T09:02:00Z","timestamp":1790586120000},"page":"7246-7273","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Excess Met1-linked ubiquitination leads to solid aggregate formation"],"prefix":"10.1038","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3841-7808","authenticated-orcid":false,"given":"Stephanie","family":"Kaypee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minori","family":"Miyasaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuto","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9779-8236","authenticated-orcid":false,"given":"Hiromi","family":"Nishimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3361-6314","authenticated-orcid":false,"given":"Jun-ichi","family":"Sakamaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7672-7722","authenticated-orcid":false,"given":"Masaaki","family":"Komatsu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0407-2768","authenticated-orcid":false,"given":"Fumiyo","family":"Ikeda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"909_CR1","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1016\/j.molcel.2024.12.015","volume":"85","author":"R Agrata","year":"2025","unstructured":"Agrata R, Komander D (2025) Ubiquitin\u2014a structural perspective. 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