Hakeem Abdulaziz, Yang Shuying
Department of Basic & Translational Sciences, School of Dental Medicine, University of Pennsylvania, USA.
Department of Basic and Translation Science, School of Dentistry, Umm Al Qura University, Saudi Arabia.
Int J Biol Sci. 2025 Jan 1;21(2):579-594. doi: 10.7150/ijbs.99010. eCollection 2025.
Inositol polyphosphate-5-phosphatase E (INPP5E) is a 5-phosphatase critically involved in diverse physiological processes, including embryonic development, neurological function, immune regulation, hemopoietic cell dynamics, and macrophage proliferation, differentiation, and phagocytosis. Mutations in cause Joubert and Meckel-Gruber syndromes in humans; these are characterized by brain malformations, microphthalmia, situs inversus, skeletal abnormalities, and polydactyly. Recent studies have demonstrated the key role of INPP5E in governing intracellular processes like endocytosis, exocytosis, vesicular trafficking, and membrane dynamics. Moreover, it regulates cellular signaling pathways by dephosphorylating the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate, phosphatidylinositol 4,5-bisphosphate, and phosphatidylinositol 3,5-bisphosphate. Despite recent advances, knowledge gaps persist regarding the function and molecular mechanism of INPP5E in various cells and species. This review integrates recent findings on the role of INPP5E in regulating cellular function, development, and the pathogenesis of various human disorders, emphasizing the molecular mechanism by which INPP5E regulates primary cilia assembly and function and critical signaling pathways. Identifying the importance of INPP5E in healthy and diseased states can advance our understanding of cellular processes and disease pathogenesis and provide a foundation for developing targeted therapeutic interventions.
肌醇多磷酸-5-磷酸酶E（INPP5E）是一种5-磷酸酶，在多种生理过程中起关键作用，包括胚胎发育、神经功能、免疫调节、造血细胞动力学以及巨噬细胞的增殖、分化和吞噬作用。该基因的突变会导致人类出现乔布综合征和梅克尔-格鲁伯综合征；其特征为脑畸形、小眼症、内脏反位、骨骼异常和多指畸形。最近的研究表明，INPP5E在调控内吞作用、外排作用、囊泡运输和膜动力学等细胞内过程中起关键作用。此外，它通过使磷脂酰肌醇-3,4,5-三磷酸、磷脂酰肌醇4,5-二磷酸和磷脂酰肌醇3,5-二磷酸的5-磷酸去磷酸化来调节细胞信号通路。尽管最近取得了进展，但关于INPP5E在各种细胞和物种中的功能及分子机制仍存在知识空白。本综述整合了关于INPP5E在调节细胞功能、发育及各种人类疾病发病机制中作用的最新研究结果，重点阐述了INPP5E调节初级纤毛组装和功能以及关键信号通路的分子机制。明确INPP5E在健康和疾病状态下的重要性，有助于我们深入理解细胞过程和疾病发病机制，并为开发针对性的治疗干预措施提供基础。
