A <scp>GJA1</scp> Variant Triggers Earlier <scp>SPG4</scp> Onset by Destabilizing Deubiquitinase <scp>VCPIP1</scp> to Lower <scp>SPASTIN</scp> Levels
The GJA1<sup>R148Q</sup> variant, although non-neurological in isolation, acts as a disease modifier that precipitates SPG4 by exacerbating SPASTIN haploinsufficiency through destabilization of VCPIP1, positioning GJA1-VCPIP1-SPASTIN signaling as a potential therapeutic axis for SPG4 treatment. © 2026 International Parkinson and Movement Disorder Society.
Authors
- Keyi Lv
- Jianhe Guo (ORCID: https://orcid.org/0000-0002-0486-5437)
- Yang Hu (ORCID: https://orcid.org/0000-0002-4508-5365)
- Yunsen He (ORCID: https://orcid.org/0000-0002-8604-6194)
- Lingzi Yang
- Dongmei Wu
- B. Y. Wu
- Min Zhong
- L Y Wang
- Qiongling Peng
- Yanling Dong
- Tongfei Liu
- Nong Xiao
- Haoran Chi
- Feifei Cheng
- Jinhua Fan
Institutions
- University of Electronic Science and Technology of China (CN)
- Army Medical University (CN)
- Dalian Medical University (CN)
- Second Affiliated Hospital of Chongqing Medical University (CN)
- Shenzhen Maternity and Child Healthcare Hospital (CN)
- Fuling Center Hospital of Chongqing (CN)
- The Affiliated Yongchuan Hospital of Chongqing Medical University (CN)
- Jiangxi Provincial Children's Hospital (CN)
- Children's Hospital of Chongqing Medical University (CN)
- Guangdong 999 Brain Hospital (CN)
- Chongqing Medical University (CN)
Publication Details
- Journal
- Movement Disorders
- Published
- 2026-02-26
- DOI
- https://doi.org/10.1002/mds.70248
- Primary Topic
- Hereditary Neurological Disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00