TAFA5, also known as FAM19A5, belongs to the TAFA chemokine-like family. It encodes small secreted proteins mainly expressed in the central nervous system and adipose tissue. It has been implicated in various biological processes such as regulating fluid homeostasis, neuronal functions related to emotional and cognitive regulation, and is also involved in inflammation-related pathways [3,2,7]. In adipose tissue, it may act as an adipokine to maintain homeostasis [6].

Genetic deletion of Fam19a5 in mice led to increased depressive-like behaviors and impaired hippocampus-dependent spatial memory, along with decreased expression of key receptors, reduced glutamate release, neuronal activity, and dendritic spine density [2]. In addition, downregulation of TAFA5 in gastric cancer cell lines inhibited cell proliferation and migration, and high TAFA5 expression was associated with poor differentiation and prognosis in gastric cancer patients [1]. In the context of type 2 diabetes subtypes, in the MOD group, TAFA5 was significantly associated with incident heart failure [4]. In obese mice, the expression of FAM19A5 was downregulated, and its down-regulation during obesity may trigger cardiometabolic diseases as it can inhibit vascular smooth muscle cell proliferation and migration [5,6].

In conclusion, TAFA5 plays essential roles in multiple biological processes. Model-based research, especially the use of KO mouse models, has revealed its significance in conditions like depression, gastric cancer, and cardiometabolic diseases. Understanding TAFA5 can potentially provide new strategies for treating these diseases.

References:

1. Hu, Zhiqing, Niu, Gengming, Ren, Jun, Hong, Runqi, Ke, Chongwei. 2019. TAFA5 promotes proliferation and migration in gastric cancer. In Molecular medicine reports, 20, 4477-4488. doi:10.3892/mmr.2019.10724. https://pubmed.ncbi.nlm.nih.gov/31702029/

2. Huang, Shiyang, Zheng, Can, Xie, Guoguang, Xing, Guo-Gang, Wang, Ying. 2020. FAM19A5/TAFA5, a novel neurokine, plays a crucial role in depressive-like and spatial memory-related behaviors in mice. In Molecular psychiatry, 26, 2363-2379. doi:10.1038/s41380-020-0720-x. https://pubmed.ncbi.nlm.nih.gov/32317715/

3. Paulsen, Sarah Juel, Christensen, Mads Tang, Vrang, Niels, Larsen, Leif Kongskov. 2008. The putative neuropeptide TAFA5 is expressed in the hypothalamic paraventricular nucleus and is regulated by dehydration. In Brain research, 1199, 1-9. doi:10.1016/j.brainres.2007.12.074. https://pubmed.ncbi.nlm.nih.gov/18275939/

4. Gurung, Resham Lal, Zheng, Huili, Lee, Bernett Teck Kwong, Coffman, Thomas M, Lim, Su Chi. 2024. Proteomics profiling and association with cardiorenal complications in type 2 diabetes subtypes in Asian population. In Diabetes research and clinical practice, 214, 111790. doi:10.1016/j.diabres.2024.111790. https://pubmed.ncbi.nlm.nih.gov/39059739/

5. Wang, Yingbao, Chen, Dixin, Zhang, Yan, Wang, Ying, Kong, Wei. 2018. Novel Adipokine, FAM19A5, Inhibits Neointima Formation After Injury Through Sphingosine-1-Phosphate Receptor 2. In Circulation, 138, 48-63. doi:10.1161/CIRCULATIONAHA.117.032398. https://pubmed.ncbi.nlm.nih.gov/29453251/

6. Wesołek-Leszczyńska, Agnieszka, Pastusiak, Katarzyna, Bogdański, Paweł, Szulińska, Monika. 2024. Can Adipokine FAM19A5 Be a Biomarker of Metabolic Disorders? In Diabetes, metabolic syndrome and obesity : targets and therapy, 17, 1651-1666. doi:10.2147/DMSO.S460226. https://pubmed.ncbi.nlm.nih.gov/38616989/

7. Kang, Dasol, Kim, Han Rae, Kim, Kwang Kon, Seong, Jae Young, Lee, Byung Ju. 2020. Brain-specific chemokine FAM19A5 induces hypothalamic inflammation. In Biochemical and biophysical research communications, 523, 829-834. doi:10.1016/j.bbrc.2019.12.119. https://pubmed.ncbi.nlm.nih.gov/31954515/