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Mono\u2010 or di\u2010ubiquitination of these molecules has been reported to stabilize aggregates and contribute to the disorders. STIP1 Homologous and U\u2010Box\u2010containing protein 1 (STUB1) is a multifunctional protein that maintains proteostasis and insulin signalling. In spinocerebellar ataxia 16 (SCAR16), an autosomal recessive neurodegenerative disease, mutations in and aggregation of STUB1 are reported. Despite the well\u2010accepted neuroprotective role of STUB1, very little is known of regulatory mechanisms that control the dynamics of STUB1 aggregate assembly. Here, we report that CARP2, a ubiquitin ligase, is a novel regulator of STUB1. CARP2 interacts and mono\u2010ubiquitinates STUB1. Furthermore, we found that CARP2 regulates STUB1 through its TPR motif, a domain that is also associated with HSP70. Modification of STUB1 by CARP2 leads to detergent\u2010insoluble aggregate formation. Importantly, pathogenic mutants of STUB1 are more prone than the wild\u2010type to CARP2\u2010mediated aggregate assembly. Hence our findings revealed CARPs (CARP1 &amp; CARP2)\u00a0as novel regulators of STUB1 and controlled its cytosolic versus aggregate dynamics.<\/jats:p>","DOI":"10.1111\/febs.16766","type":"journal-article","created":{"date-parts":[[2023,2,28]],"date-time":"2023-02-28T10:10:05Z","timestamp":1677579005000},"page":"3580-3594","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["CARPs regulate STUB1 and its pathogenic mutants aggregation kinetics by mono\u2010ubiquitination"],"prefix":"10.1111","volume":"290","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6504-0578","authenticated-orcid":false,"given":"Rahul","family":"Sharma","sequence":"first","affiliation":[{"name":"School of Biology Indian Institute of Science Education and Research Thiruvananthapuram  India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Prema","family":"Mondal","sequence":"additional","affiliation":[{"name":"School of Biology 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