IgLON5, a gene encoding a cell adhesion molecule, is involved in cell-cell interactions and plays a role in the nervous system. It may participate in pathways related to neuronal development, function, and communication. Understanding its function is crucial for insights into normal neural processes and related disorders [1-10].

Anti-IgLON5 disease is an autoimmune disorder associated with autoantibodies against IgLON5. It has a broad clinical spectrum, including sleep disorders, bulbar symptoms, movement disorders, and cognitive decline. The disease shows characteristics of both autoimmunity and neurodegeneration. Neuropathological examination reveals a tauopathy preferentially affecting the hypothalamus and brainstem tegmentum. Basic studies suggest that IgLON5 antibody-induced neuronal damage is irreversible, indicating a potential link between autoimmunity and neurodegeneration [1,2,3]. Low levels of neurofilament light chain in serum and cerebrospinal fluid at disease onset could be a predictor of immunotherapy response [2].

In conclusion, IgLON5 is important for normal nervous system function. Studies on anti-IgLON5 disease, though not directly from KO/CKO mouse models in the provided references, have shown that IgLON5 autoantibodies are associated with a complex disorder with features of autoimmunity and neurodegeneration. Understanding IgLON5 is key to further exploring the pathogenesis of this disease and potentially developing better treatment strategies [1,2,3].

References:

1. Zhang, Yi-Zong Heng, Ni, You, Gao, Yi-Ning, Hu, Ji, Chen, Sheng. . Anti-IgLON5 disease: a novel topic beyond neuroimmunology. In Neural regeneration research, 18, 1017-1022. doi:10.4103/1673-5374.355742. https://pubmed.ncbi.nlm.nih.gov/36254983/

2. Gaig, Carles, Sabater, Lidia. 2024. New knowledge on anti-IgLON5 disease. In Current opinion in neurology, 37, 316-321. doi:10.1097/WCO.0000000000001271. https://pubmed.ncbi.nlm.nih.gov/38563128/

3. Graus, Francesc, Sabater, Lidia, Gaig, Carles, Dalmau, Josep O, Santamaria, Joan. 2024. Anti-IgLON5 Disease 10 Years Later: What We Know and What We Do Not Know. In Neurology(R) neuroimmunology & neuroinflammation, 12, e200353. doi:10.1212/NXI.0000000000200353. https://pubmed.ncbi.nlm.nih.gov/39705634/