Lancl2, or lanthionine synthetase C-like 2, is a gene with diverse functions. It exhibits glutathionylation activity and is involved in neutralizing reactive electrophiles. LANCL2 also binds to abscisic acid (ABA), playing a role in the ABA-signaling pathway. It is expressed in the central nervous system, peripheral tissues, and is particularly important in immunoregulation, redox homeostasis, and cell proliferation-related pathways [3,5].

Genetic ablation of Lancl2 in mice leads to severe inflammatory phenotypes in inflammatory bowel disease (IBD) and lupus, highlighting its crucial role in maintaining immune balance [1,6]. In Lancl2 knockout mice, sperm parameters are injured, with disrupted testicular redox homeostasis and acrosomal maturation defects, indicating its importance in testicular function [2]. In EGFR-mutant lung adenocarcinoma cell lines, knockdown of Lancl2 reduces cell proliferation and enhances apoptosis, suggesting its role in promoting tumorigenesis [4].

In conclusion, Lancl2 is essential for various biological functions. Its knockout mouse models have revealed its significance in autoimmune diseases like IBD and lupus, testicular function, and cancer-related processes. Understanding Lancl2 provides insights into disease mechanisms and potential therapeutic targets for these conditions.

References:

1. Tubau-Juni, Nuria, Hontecillas, Raquel, Leber, Andrew J, Alva, Sameeksha S, Bassaganya-Riera, Josep. . Treating Autoimmune Diseases With LANCL2 Therapeutics: A Novel Immunoregulatory Mechanism for Patients With Ulcerative Colitis and Crohn's Disease. In Inflammatory bowel diseases, 30, 671-680. doi:10.1093/ibd/izad258. https://pubmed.ncbi.nlm.nih.gov/37934790/

2. Zhao, Yanling, Wang, Jichen, Shi, Shuai, Chen, Zhengli, Huang, Chao. 2024. LanCL2 Implicates in Testicular Redox Homeostasis and Acrosomal Maturation. In Antioxidants (Basel, Switzerland), 13, . doi:10.3390/antiox13050534. https://pubmed.ncbi.nlm.nih.gov/38790639/

3. Scarano, Naomi, Di Palma, Francesco, Origlia, Nicola, Cichero, Elena, Cavalli, Andrea. 2023. New Insights into the LANCL2-ABA Binding Mode towards the Evaluation of New LANCL Agonists. In Pharmaceutics, 15, . doi:10.3390/pharmaceutics15122754. https://pubmed.ncbi.nlm.nih.gov/38140095/

4. Lou, Yuqing, Xu, Jianlin, Zhang, Yanwei, Lu, Jun, Han, Baohui. 2021. Akt kinase LANCL2 functions as a key driver in EGFR-mutant lung adenocarcinoma tumorigenesis. In Cell death & disease, 12, 170. doi:10.1038/s41419-021-03439-8. https://pubmed.ncbi.nlm.nih.gov/33568630/

5. Sturla, Laura, Fresia, Chiara, Guida, Lucrezia, De Flora, Antonio, Zocchi, Elena. 2009. LANCL2 is necessary for abscisic acid binding and signaling in human granulocytes and in rat insulinoma cells. In The Journal of biological chemistry, 284, 28045-28057. doi:10.1074/jbc.M109.035329. https://pubmed.ncbi.nlm.nih.gov/19667068/

6. Leber, Andrew, Hontecillas, Raquel, Tubau-Juni, Nuria, Fitch, Sarah N, Bassaganya-Riera, Josep. . Immunometabolic Mechanisms of LANCL2 in CD4+ T Cells and Phagocytes Provide Protection from Systemic Lupus Erythematosus. In Journal of immunology (Baltimore, Md. : 1950), 213, 1429-1440. doi:10.4049/jimmunol.2400127. https://pubmed.ncbi.nlm.nih.gov/39365106/