Emerging Roles of PSTPIP2 in Autoimmunity: From Mechanism to Therapeutic Implications
7 affiliations
- 1Orthopaedic Research Institute of Hebei Province Shijiazhuang People's Republic of China
- 2Engineering Research Center of Orthopedic Minimally Invasive Intelligent Equipment Ministry of Education Shijiazhuang Hebei China
- 3Department of Otolaryngology The Third Hospital of Hebei Medical University Shijiazhuang People's Republic of China
- 4Department of Orthopedic Oncology Third Hospital of Hebei Medical University Shijiazhuang People's Republic of China
- 5Key Laboratory of Biomechanics of Hebei Province Shijiazhuang China
- 6NHC Key Laboratory of Intelligent Orthopaedic Equipment Shijiazhuang China
- 7Key Laboratory of Precise Assessment, Diagnosis, and Treament of Soft Tissue Injury of Hebei Province Shijiazhuang Hebei China
Abstract
Autoimmune and autoinflammatory diseases are characterised by dysregulated immune activation and persistent inflammation, yet effective mechanism‐based therapeutic targets remain limited. Proline‐serine–threonine phosphatase‐interacting protein 2 (PSTPIP2), a membrane–cytoskeleton‐associated adaptor protein predominantly expressed in myeloid cells, has emerged as an important endogenous regulator of inflammatory responses. This review summarises the molecular structure, expression pattern and biological functions of PSTPIP2, with particular emphasis on its role in coordinating cytoskeletal remodelling, inflammatory signalling and immune‐cell behaviour. We further discuss the major mechanisms through which PSTPIP2 regulates disease progression, including suppression of IL‐1β maturation, inhibition of NF‐κB and ERK signalling, modulation of macrophage polarisation and control of osteoclast‐associated bone remodelling. In addition, recent advances in understanding the involvement of PSTPIP2 in chronic multifocal osteomyelitis, rheumatoid arthritis, SAPHO syndrome and bullous pemphigoid are reviewed, together with evidence from PSTPIP2‐deficient models that has provided important mechanistic and translational insights. Finally, the potential value of PSTPIP2 as a biomarker and therapeutic target is highlighted. Overall, PSTPIP2 represents a critical immunoregulatory node linking cytoskeletal organisation to inflammatory control, and further investigation of its molecular functions may facilitate the development of precision therapies for autoimmune and autoinflammatory diseases.
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BibTeX
@article{zhang2026emerging,
title = {{Emerging Roles of PSTPIP2 in Autoimmunity: From Mechanism to Therapeutic Implications}},
author = {Erdong Zhang and Fengyu Liu and Yongle Wei and Guoqiang Li and Liujie Zheng and Lin Jin and Feng Luan and Yingze Zhang and Ling Wang and Zhiyong Hou},
journal = {Immunology},
year = {2026},
month = aug,
doi = {10.1111/imm.70188},
url = {https://doi.org/10.1111/imm.70188},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Emerging Roles of PSTPIP2 in Autoimmunity: From Mechanism to Therapeutic Implications
AU - Erdong Zhang
AU - Fengyu Liu
AU - Yongle Wei
AU - Guoqiang Li
AU - Liujie Zheng
AU - Lin Jin
AU - Feng Luan
AU - Yingze Zhang
AU - Ling Wang
AU - Zhiyong Hou
PY - 2026
DA - 2026/08/13
JO - Immunology
DO - 10.1111/imm.70188
UR - https://doi.org/10.1111/imm.70188
AB - Autoimmune and autoinflammatory diseases are characterised by dysregulated immune activation and persistent inflammation, yet effective mechanism‐based therapeutic targets remain limited. Proline‐serine–threonine phosphatase‐interacting protein 2 (PSTPIP2), a membrane–cytoskeleton‐associated adaptor protein predominantly expressed in myeloid cells, has emerged as an important endogenous regulator of inflammatory responses. This review summarises the molecular structure, expression pattern and biological functions of PSTPIP2, with particular emphasis on its role in coordinating cytoskeletal remodelling, inflammatory signalling and immune‐cell behaviour. We further discuss the major mechanisms through which PSTPIP2 regulates disease progression, including suppression of IL‐1β maturation, inhibition of NF‐κB and ERK signalling, modulation of macrophage polarisation and control of osteoclast‐associated bone remodelling. In addition, recent advances in understanding the involvement of PSTPIP2 in chronic multifocal osteomyelitis, rheumatoid arthritis, SAPHO syndrome and bullous pemphigoid are reviewed, together with evidence from PSTPIP2‐deficient models that has provided important mechanistic and translational insights. Finally, the potential value of PSTPIP2 as a biomarker and therapeutic target is highlighted. Overall, PSTPIP2 represents a critical immunoregulatory node linking cytoskeletal organisation to inflammatory control, and further investigation of its molecular functions may facilitate the development of precision therapies for autoimmune and autoinflammatory diseases.
SN - 0019-2805
SN - 1365-2567
ER -