Tppp3, also known as tubulin polymerization-promoting protein family member 3, is involved in modulating microtubule dynamics and stability [7]. It is associated with various biological processes and disease-related pathways. Genetic models, such as mouse models, have been crucial for studying its functions.

In tendon-related studies, Tppp3+Pdgfra+ cells were identified as potential tendon stem cells. Inactivation of Pdgfra in Tppp3+ cells blocked tendon regeneration, highlighting the role of Tppp3-expressing cells in tendon repair [1]. In heterotopic ossification, Tppp3-expressing synovial/tendon sheath progenitor cells contributed to heterotopic bone formation after trauma [2]. In glioblastoma, up-regulation of TPPP3 increased glioblastoma cell migration, invasion, and proliferation, while its inhibition had the opposite effects, and it affected the epithelial-mesenchymal transition via Snail1 [3]. In endometrial carcinoma, TPPP3 was highly expressed, and its knockdown suppressed cell proliferation, migration, and invasion [4]. In head and neck squamous carcinoma (HNSC), TPPP3 expression was reduced, and it was associated with prognosis and immune infiltration, negatively correlating with the infiltration of certain immune cells [5]. In the optic nerve, Tppp3 overexpression promoted axon regeneration and RGC survival after optic nerve crush [6]. In Parkinson's disease-related research, TPPP3 modulated microtubule organization, did not bind to alpha-synuclein, and counteracted the formation of the TPPP1-SYN pathological complex [7]. In oral squamous cell carcinoma (OSCC), TPPP3 was less expressed, and it inhibited cell proliferation and migration, being associated with good prognosis [8]. In embryo-related studies, uterine TPPP3 was important for embryo implantation and decidualization, with its knockdown leading to implantation failure and suppression of decidualization-related markers and signaling pathways [9,10].

In conclusion, Tppp3 plays diverse and essential biological functions, revealed through model-based research. In particular, mouse models with genetic manipulations of Tppp3 have provided insights into its roles in tendon regeneration, heterotopic ossification, cancer development, and embryo-related processes, which are crucial for understanding the underlying mechanisms of these diseases and biological processes and may offer potential therapeutic targets.

References:

1. Harvey, Tyler, Flamenco, Sara, Fan, Chen-Ming. 2019. A Tppp3+Pdgfra+ tendon stem cell population contributes to regeneration and reveals a shared role for PDGF signalling in regeneration and fibrosis. In Nature cell biology, 21, 1490-1503. doi:10.1038/s41556-019-0417-z. https://pubmed.ncbi.nlm.nih.gov/31768046/

2. Yea, Ji-Hye, Gomez-Salazar, Mario, Onggo, Sharon, Levi, Benjamin, James, Aaron W. 2023. Tppp3+ synovial/tendon sheath progenitor cells contribute to heterotopic bone after trauma. In Bone research, 11, 39. doi:10.1038/s41413-023-00272-x. https://pubmed.ncbi.nlm.nih.gov/37479686/

3. Xu, Xu, Hou, Yunan, Long, Niya, Qi, Xiaolan, Chu, Liangzhao. 2023. TPPP3 promote epithelial-mesenchymal transition via Snail1 in glioblastoma. In Scientific reports, 13, 17960. doi:10.1038/s41598-023-45233-w. https://pubmed.ncbi.nlm.nih.gov/37863960/

4. Shen, Aiqun, Tong, Xiaowen, Li, Huaifang, Ma, Hanbo, Ouyang, Yiqin. 2021. TPPP3 inhibits the proliferation, invasion and migration of endometrial carcinoma targeted with miR-1827. In Clinical and experimental pharmacology & physiology, 48, 890-901. doi:10.1111/1440-1681.13456. https://pubmed.ncbi.nlm.nih.gov/33644928/

5. Yang, Zheng, Li, Xiaohong, Li, Jingyu, Zhang, Liqian, Mo, Wuning. 2020. TPPP3 Associated with Prognosis and Immune Infiltrates in Head and Neck Squamous Carcinoma. In BioMed research international, 2020, 3962146. doi:10.1155/2020/3962146. https://pubmed.ncbi.nlm.nih.gov/33083464/

6. Rao, Mishal, Luo, Ziming, Liu, Chia-Chun, Sahel, José-Alain, Chang, Kun-Che. 2024. Tppp3 is a novel molecule for retinal ganglion cell identification and optic nerve regeneration. In Acta neuropathologica communications, 12, 204. doi:10.1186/s40478-024-01917-6. https://pubmed.ncbi.nlm.nih.gov/39734233/

7. Oláh, Judit, Lehotzky, Attila, Szénási, Tibor, Berki, Tímea, Ovádi, Judit. 2022. Modulatory Role of TPPP3 in Microtubule Organization and Its Impact on Alpha-Synuclein Pathology. In Cells, 11, . doi:10.3390/cells11193025. https://pubmed.ncbi.nlm.nih.gov/36230985/

8. Xiao, Ting, Rahhal, Omar, Wang, Liping, Qi, Lu, Tang, Zhangui. 2025. TPPP3, a Good Prognostic Indicator, Suppresses Cell Proliferation and Migration in OSCC. In International dental journal, 75, 970-983. doi:10.1016/j.identj.2024.09.035. https://pubmed.ncbi.nlm.nih.gov/39814636/

9. Shukla, Vinay, Popli, Pooja, Kaushal, Jyoti Bala, Gupta, Kanchan, Dwivedi, Anila. . Uterine TPPP3 plays important role in embryo implantation via modulation of β-catenin. In Biology of reproduction, 99, 982-999. doi:10.1093/biolre/ioy136. https://pubmed.ncbi.nlm.nih.gov/29901777/

10. Shukla, Vinay, Kaushal, Jyoti Bala, Sankhwar, Pushplata, Manohar, Murli, Dwivedi, Anila. . Inhibition of TPPP3 attenuates β-catenin/NF-κB/COX-2 signaling in endometrial stromal cells and impairs decidualization. In The Journal of endocrinology, 240, 417-429. doi:10.1530/JOE-18-0459. https://pubmed.ncbi.nlm.nih.gov/30667362/