Ppef1, the protein phosphatase with EF-hand domain 1, is a calmodulin-binding protein. It has been associated with multiple biological processes. In spermatozoa, it may be involved in sperm capacitation, binding to the zona pellucida, and motility, as it localizes in the neck and acrosome areas of sperm and co-immunoprecipitated proteins show enrichment in these processes [4]. In C. elegans, the ortholog PEF-1 is a ciliary protein that depends on transition zone proteins for its compartmentalization within cilia, and its absence leads to ciliary structural defects and anomalies in cilium-dependent behaviors [6].

In breast cancer, Ppef1 has been studied as a potential biomarker. Its transcriptional levels are higher in breast cancer tissues compared to normal or adjacent normal tissues. Higher Ppef1 expression is negatively associated with overall survival, all events-free and metastatic recurrence-free survival, and is an independent risk factor for unfavorable prognosis. It also promotes breast cancer progression and can be used as a non-invasive diagnostic marker, and combined with traditional tumor markers, it can enhance diagnostic accuracy [1]. In stomach adenocarcinoma, overexpression of Ppef1 is associated with infiltration by antigen-presenting cells, and it is a potential mRNA vaccine candidate [3]. In Alzheimer's disease, Ppef1 is identified as one of the hub genes associated with disulfidptosis, and a gene set including it shows significant enrichment for AD-related pathways [2]. In bronchial asthma, transcriptomic analysis suggests that Zhichuanling injection may alleviate asthma symptoms by modulating Ppef1 among other genes [5].

In conclusion, Ppef1 is involved in various biological processes such as sperm-related functions and ciliary-associated behaviors in model organisms. In diseases, it shows potential as a biomarker in breast cancer, a vaccine candidate in stomach adenocarcinoma, and is associated with Alzheimer's disease and bronchial asthma. These findings from different research models contribute to understanding its role in normal biology and disease conditions.

References:

1. Ye, Ting, Wan, Xue, Li, Jingyuan, Li, Guangrong, Liu, Jinbo. 2020. The Clinical Significance of PPEF1 as a Promising Biomarker and Its Potential Mechanism in Breast Cancer. In OncoTargets and therapy, 13, 199-214. doi:10.2147/OTT.S229432. https://pubmed.ncbi.nlm.nih.gov/32021267/

2. Huang, Lei, Li, Zhengtai, Lv, Yitong, Li, Yingji, Yu, Changyuan. 2024. Unveiling disulfidptosis-related biomarkers and predicting drugs in Alzheimer's disease. In Scientific reports, 14, 20185. doi:10.1038/s41598-024-70893-7. https://pubmed.ncbi.nlm.nih.gov/39215110/

3. You, Weiqiang, Ouyang, Jian, Cai, Zerong, Chen, Yufeng, Wu, Xiaojian. 2022. Comprehensive Analyses of Immune Subtypes of Stomach Adenocarcinoma for mRNA Vaccination. In Frontiers in immunology, 13, 827506. doi:10.3389/fimmu.2022.827506. https://pubmed.ncbi.nlm.nih.gov/35874675/

4. Lavoie-Ouellet, Camille, Clark, Marie-Ève, Ruiz, Juliana, Saindon, Andrée-Anne, Leclerc, Pierre. 2021. The protein phosphatase with EF-hand domain 1 is a calmodulin-binding protein that interacts with proteins involved in sperm capacitation, binding to the zona pellucida, and motility. In Molecular reproduction and development, 88, 302-317. doi:10.1002/mrd.23467. https://pubmed.ncbi.nlm.nih.gov/33783058/

5. Ren, Kerui, Niu, Bo, Liang, Huaduan, Zhao, Fang, Cao, Zhengyu. 2025. Zhichuanling injection improves bronchial asthma by attenuation airway inflammation and epithelia-mesenchymal transition. In Journal of ethnopharmacology, 344, 119540. doi:10.1016/j.jep.2025.119540. https://pubmed.ncbi.nlm.nih.gov/40020793/

6. Barbelanne, Marine, Lu, Yun, Kumar, Keerthana, Shaham, Shai, Leroux, Michel R. 2024. C. elegans PPEF-type phosphatase (Retinal degeneration C ortholog) functions in diverse classes of cilia to regulate nematode behaviors. In Scientific reports, 14, 28347. doi:10.1038/s41598-024-79057-z. https://pubmed.ncbi.nlm.nih.gov/39550471/