ZFYVE28, also known as LST2, contains a FYVE domain and is involved in multiple biological processes. It plays a role in endosomal regulation, influencing the conversion between different endosome types, and is associated with pathways such as the insulin signaling pathway, EGFR-signaling pathway, and vesicle-mediated transport [1,2,3]. It may also be involved in processes related to sleep regulation, cancer-related pathways, and glucose and insulin metabolism [4,5,6]. Genetic models like mouse knockout models are valuable for studying its functions.

In insulin-related research, Zfyve28 knockout in mice significantly improves insulin sensitivity and related indicators. Mechanistically, ZFYVE28 promotes the conversion of early to late endosomes, leading to the degradation of phosphorylated insulin receptor, thus mediating insulin resistance [1]. In podocytes, ZFYVE28-deficient mice show normal kidney development and maintenance of the filtration barrier, but ZFYVE28 overexpression promotes EGF-signaling in cultured podocytes [2].

In conclusion, ZFYVE28 is essential in endosomal regulation and has implications in insulin resistance and EGFR-signaling in podocytes. The gene knockout mouse models have been crucial in revealing its role in these disease-related areas, providing potential therapeutic targets for improving insulin sensitivity and understanding glomerular disease processes [1,2].

References:

1. Yu, Liang, Xu, Mengchen, Yan, Yupeng, Hui, Rutai, Wang, Yibo. 2023. ZFYVE28 mediates insulin resistance by promoting phosphorylated insulin receptor degradation via increasing late endosomes production. In Nature communications, 14, 6833. doi:10.1038/s41467-023-42657-w. https://pubmed.ncbi.nlm.nih.gov/37884540/

2. Zambrano, Sonia, Rodriguez, Patricia Q, Guo, Jing, Schwarz, Angelina, Patrakka, Jaakko. 2018. FYVE domain-containing protein ZFYVE28 regulates EGFR-signaling in podocytes but is not critical for the function of filtration barrier in mice. In Scientific reports, 8, 4712. doi:10.1038/s41598-018-23104-z. https://pubmed.ncbi.nlm.nih.gov/29549365/

3. Yan, Fei, Tao, Jing, Liu, Jie, Chen, Yongliang, Huang, Zongju. 2025. Cross-tissue transcriptome-wide association study reveals novel psoriasis susceptibility genes. In Journal of translational autoimmunity, 10, 100286. doi:10.1016/j.jtauto.2025.100286. https://pubmed.ncbi.nlm.nih.gov/40206863/

4. Huang, Huiyan, Zhu, Yong, Eliot, Melissa N, Carskadon, Mary A, Hart, Anne C. . Combining Human Epigenetics and Sleep Studies in Caenorhabditis elegans: A Cross-Species Approach for Finding Conserved Genes Regulating Sleep. In Sleep, 40, . doi:10.1093/sleep/zsx063. https://pubmed.ncbi.nlm.nih.gov/28431118/

5. Liang, Zhuo-Zhi, Zhang, Yi-Xin, Zhu, Rui-Mei, Tang, Lu-Ying, Ren, Ze-Fang. 2021. Identification of epigenetic modifications mediating the antagonistic effect of selenium against cadmium-induced breast carcinogenesis. In Environmental science and pollution research international, 29, 22056-22068. doi:10.1007/s11356-021-17355-z. https://pubmed.ncbi.nlm.nih.gov/34773240/

6. Lai, Wanlin, Wu, Yiming, Sha, Leihao, Zhu, Xi, Chen, Lei. 2023. Identifying Genetic Factors of Polycystic Ovary Syndrome in Women with Epilepsy: A Whole-Genome Sequencing Study. In Neuroendocrinology, 114, 223-233. doi:10.1159/000534531. https://pubmed.ncbi.nlm.nih.gov/37827139/