Ankfy1, also known as ankyrin repeat and FYVE domain containing 1, is a protein-coding gene. It is involved in multiple biological processes. It participates in endocytosis as a double zinc finger protein. In the context of autophagy, it bridges ATG2A-mediated lipid transfer from endosomes to phagophores, which is crucial for autophagosome biogenesis [1]. It also interacts with RAB5, an endosomal regulator, and is associated with pathways related to cell proliferation, migration, and organ development [5].

Gene knockout mouse models have provided insights into Ankfy1 function. Ankfy1 knockout mice start to show abnormal cerebellum with reduced vermis size and defective motor function at 9-month-old due to loss of cerebellar Purkinje cells, suggesting its importance in maintaining these cells [2]. In neural development, Ankfy1 seems dispensable in mixed-genetic background null mice, but lethal in pure C57/BL6 inbred mice embryos [4]. In retinal endothelial cells, ANKFY1 knockdown suppresses cell growth and migration, revealing its role in angiogenesis-related processes [3]. In a new mouse model of autosomal recessive spastic ataxia of Charlevoix-Saguenay, Ankfy1 heterozygous mice display progressive motor and cerebellar nerve dysfunction, Purkinje cell loss, and abnormal neurotrophic factor expression.

In summary, Ankfy1 plays essential roles in processes such as autophagy, cell proliferation, migration, and the maintenance of specific cell types like cerebellar Purkinje cells. The study of Ankfy1 knockout mouse models has been valuable in understanding its functions in neurodegenerative diseases like autosomal recessive spastic ataxia of Charlevoix-Saguenay, as well as in conditions related to angiogenesis and neural development.

References:

1. Wei, Bin, Fu, Yuhui, Li, Xiuzhi, Liu, Xiaoxia, Zhong, Qing. 2024. ANKFY1 bridges ATG2A-mediated lipid transfer from endosomes to phagophores. In Cell discovery, 10, 43. doi:10.1038/s41421-024-00659-y. https://pubmed.ncbi.nlm.nih.gov/38622126/

2. Chang, Liansheng, Soomro, Shahid Hussain, Zhang, Hongfeng, Fu, Hui. 2021. Ankfy1 Is Involved in the Maintenance of Cerebellar Purkinje Cells. In Frontiers in cellular neuroscience, 15, 648801. doi:10.3389/fncel.2021.648801. https://pubmed.ncbi.nlm.nih.gov/33796010/

3. Tanaka, Miruto, Nakamura, Shinsuke, Maekawa, Masashi, Higashiyama, Shigeki, Hara, Hideaki. 2020. ANKFY1 is essential for retinal endothelial cell proliferation and migration via VEGFR2/Akt/eNOS pathway. In Biochemical and biophysical research communications, 533, 1406-1412. doi:10.1016/j.bbrc.2020.10.032. https://pubmed.ncbi.nlm.nih.gov/33092793/

4. Weng, Chao, Ding, Man, Chang, Lian-Sheng, Lu, Zu-Neng, Fu, Hui. . Ankfy1 is dispensable for neural stem/precursor cell development. In Neural regeneration research, 11, 1804-1809. doi:10.4103/1673-5374.194750. https://pubmed.ncbi.nlm.nih.gov/28123425/

5. Hermle, Tobias, Schneider, Ronen, Schapiro, David, Shril, Shirlee, Hildebrandt, Friedhelm. 2018. GAPVD1 and ANKFY1 Mutations Implicate RAB5 Regulation in Nephrotic Syndrome. In Journal of the American Society of Nephrology : JASN, 29, 2123-2138. doi:10.1681/ASN.2017121312. https://pubmed.ncbi.nlm.nih.gov/29959197/

6. Zhang, Luyan, Cheng, Xueqin, Wang, Chunli, Zheng, Bixia, Zhang, Aihua. 2024. Compound heterozygous variants of ANKFY1 in a child with infantile-onset proteinuria and movement disorder. In Clinical kidney journal, 17, sfae124. doi:10.1093/ckj/sfae124. https://pubmed.ncbi.nlm.nih.gov/38915441/

7. Ding, Man, Weng, Chao, Fan, Shanghua, Cao, Qian, Lu, Zuneng. 2017. Purkinje Cell Degeneration and Motor Coordination Deficits in a New Mouse Model of Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay. In Frontiers in molecular neuroscience, 10, 121. doi:10.3389/fnmol.2017.00121. https://pubmed.ncbi.nlm.nih.gov/28588446/