Lrrc4, also named netrin-G ligand 2 (NGL-2), is a member of the NetrinGs ligands (NGLs) family and the leucine-rich repeat superfamily. It is highly and specifically expressed in the brain. Lrrc4 is involved in multiple biological processes, such as promoting axon differentiation, mediating synapse formation and plasticity, and is crucial for information input and memory storage in the hippocampus. In the context of diseases, it acts as a suppressor gene for gliomas and is involved in regulatory loops that inhibit glioblastoma cell proliferation and invasion [1].

In experimental autoimmune encephalomyelitis (EAE) mouse models, Lrrc4 knockout led to quickened and exacerbated disease progression, more severe myelin degeneration, and leukocyte infiltration into the spinal cords. This indicates that Lrrc4 has a neuron-protective role in EAE, potentially serving as a target for multiple sclerosis treatment [2]. In glioblastoma, Lrrc4-null cells showed disordered RAP1GAP gene expression and increased cellular movement, while re-expression of Lrrc4 suppressed tumors, suggesting its potential for targeted glioblastoma treatment [3].

In summary, Lrrc4 is essential for nervous system development and function. Gene knockout studies in mouse models have revealed its roles in protecting neurons in EAE and suppressing tumor-related processes in glioblastoma, highlighting its significance in understanding and potentially treating these diseases.

References:

1. Deng, Kun, Wu, Minghua. 2023. Leucine-rich repeats containing 4 protein (LRRC4) in memory, psychoneurosis, and glioblastoma. In Chinese medical journal, 136, 4-12. doi:10.1097/CM9.0000000000002441. https://pubmed.ncbi.nlm.nih.gov/36780420/

2. Zhang, Yan, Li, Di, Zeng, Qiuming, Yang, Huan, Wu, Minghua. 2021. LRRC4 functions as a neuron-protective role in experimental autoimmune encephalomyelitis. In Molecular medicine (Cambridge, Mass.), 27, 44. doi:10.1186/s10020-021-00304-4. https://pubmed.ncbi.nlm.nih.gov/33932995/

3. Liu, Yang, Xu, Gang, Fu, Haijuan, Shang, Yujie, Wu, Minghua. 2023. Membrane-bound transcription factor LRRC4 inhibits glioblastoma cell motility. In International journal of biological macromolecules, 246, 125590. doi:10.1016/j.ijbiomac.2023.125590. https://pubmed.ncbi.nlm.nih.gov/37385320/