Ftl1, the ferritin light chain 1 gene, plays a crucial role in iron metabolism. Ferritin, assembled from Ftl1-encoded light chains and ferritin heavy chain 1 (Fth1), is a key complex for iron storage and reduction, which is essential for maintaining iron homeostasis in various biological systems [2,4].

Mutations in Ftl1 can lead to neuroferritinopathy, an adult-onset progressive movement disorder. For instance, the 460insA mutation disrupts the ferritin dodecahedron structure, causing ferritin and iron accumulation mainly in central neurons [1,5]. In ischemic stroke, Ftl1 promotes microglia activation, as well as the production of inflammatory factors and chemokines, aggravating brain tissue damage [3]. In addition, in the context of ferroptosis, Ftl1 is transcriptionally regulated by the transcription factor BACH1, and its expression is associated with the control of this iron-dependent programmed cell death event [2].

In summary, Ftl1 is vital for iron homeostasis. Studies on Ftl1, especially those related to its mutations in mouse models (although not specifically mentioned as KO/CKO in the provided references), have revealed its role in neurodegenerative diseases like neuroferritinopathy and in conditions such as ischemic stroke and ferroptosis, providing insights into potential disease mechanisms and treatment targets [1,2,3,5].

References:

1. Burn, John, Chinnery, Patrick F. . Neuroferritinopathy. In Seminars in pediatric neurology, 13, 176-81. doi:. https://pubmed.ncbi.nlm.nih.gov/17101456/

2. Nishizawa, Hironari, Matsumoto, Mitsuyo, Shindo, Tomohiko, Shimokawa, Hiroaki, Igarashi, Kazuhiko. 2019. Ferroptosis is controlled by the coordinated transcriptional regulation of glutathione and labile iron metabolism by the transcription factor BACH1. In The Journal of biological chemistry, 295, 69-82. doi:10.1074/jbc.RA119.009548. https://pubmed.ncbi.nlm.nih.gov/31740582/

3. Shi, Cheng-Long, Han, Xiu-Li, Chen, Jing-Ce, Min, Xiao-Li, Gao, Yong-Jun. 2024. Single-nucleus transcriptome unveils the role of ferroptosis in ischemic stroke. In Heliyon, 10, e32727. doi:10.1016/j.heliyon.2024.e32727. https://pubmed.ncbi.nlm.nih.gov/38994078/

4. Tortuyaux, Romain, Avila-Gutierrez, Katia, Oudart, Marc, Escartin, Carole, Cohen-Salmon, Martine. 2023. Physiopathological changes of ferritin mRNA density and distribution in hippocampal astrocytes in the mouse brain. In Journal of neurochemistry, 164, 847-857. doi:10.1111/jnc.15747. https://pubmed.ncbi.nlm.nih.gov/36562685/

5. Kumar, Niraj, Rizek, Philippe, Jog, Mandar. 2016. Neuroferritinopathy: Pathophysiology, Presentation, Differential Diagnoses and Management. In Tremor and other hyperkinetic movements (New York, N.Y.), 6, 355. doi:10.7916/D8KK9BHF. https://pubmed.ncbi.nlm.nih.gov/27022507/