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However, the molecular mechanisms underlying these perturbations and how they are directly regulated remain unclear. B cell receptor-associated protein 31 (BAP31), which is highly expressed in the ER, has been shown to participate mainly in regulating ER stress and apoptosis. Here, our results showed that BAP31 expression was dramatically decreased in PD. Notably, overexpression of BAP31 exerted neuroprotective effects by inhibiting ER stress and apoptosis in vitro and in vivo, whereas BAP31 siRNA strongly abolished these effects. Interestingly, 4-phenylbutyric acid (4-PBA), the ER stress inhibitor, reversed the detrimental effect of BAP31 knockdown in vitro. Mutations in PTEN-induced putative kinase 1 (PINK1) are known to cause autosomal recessive early-onset PD. PINK1 has been implicated in protein phosphorylation pathways that are associated with ER stress and apoptosis. Bioinformatics analysis and our results demonstrated that PINK1 interacts with BAP31 and phosphorylates it at the Ser 142 residue. Furthermore, the protective effects of PINK1 overexpression against ER stress-mediated apoptosis were abolished by BAP31 interference or BAP31-S142A and strengthened by BAP31-S142E. Overall, the present study suggests that BAP31 overexpression exerts neuroprotective effects by inhibiting ER stress-induced apoptosis. Regulation of the PINK1\/BAP31 pathway may be a beneficial strategy for PD.<\/jats:p>","DOI":"10.1038\/s41419-025-07907-3","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T06:55:55Z","timestamp":1759128955000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["BAP31 represses endoplasmic reticulum stress-mediated apoptosis and alleviates neurodegeneration in Parkinson\u2019s disease"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-4843-0495","authenticated-orcid":false,"given":"Yan","family":"Qin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghao","family":"Chi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junzhen","family":"Jia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhecheng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4000-1534","authenticated-orcid":false,"given":"Junjun","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihong","family":"Yao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,29]]},"reference":[{"key":"7907_CR1","doi-asserted-by":"publisher","first-page":"S3","DOI":"10.3233\/JPD-181474","volume":"8","author":"ER Dorsey","year":"2018","unstructured":"Dorsey ER, Sherer T, Okun MS, Bloem BR. 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