Elfn2, or extracellular leucine rich repeat and fibronectin type III domain containing 2, is a gene with diverse functions. It acts as a postsynaptic cell adhesion molecule, playing a crucial role in controlling group III metabotropic glutamate receptors (mGluRs) in the brain, which is essential for glutamatergic synaptic transmission and normal brain function. It is also involved in processes like chromatin remodeling during spermiogenesis, cell autophagy in glioblastoma (GBM), and the regulation of gastric cancer progression [1,2,3,4].

In mice, loss of Elfn2 leads to selective downregulation of group III mGluRs and dysregulated glutamatergic synaptic transmission, resulting in neuropsychiatric manifestations such as seizure susceptibility, hyperactivity, and anxiety/compulsivity. These phenotypes can be rescued by pharmacological augmentation of group III mGluRs, highlighting the importance of Elfn2 in maintaining normal brain function [2]. In testis-specific Ddx43 knockout mice, which show male infertility due to chromatin remodeling defects during spermiogenesis, Elfn2 is identified as a DDX43-targeted hub gene, suggesting its role in this process [1].

In conclusion, Elfn2 is essential for normal brain function, especially in regulating group III mGluRs, and is also involved in spermatogenesis and certain cancer-related processes. The use of gene knockout mouse models has been instrumental in revealing these functions, providing insights into its role in neuropsychiatric disorders, male infertility, and cancer.

References:

1. Tan, Huanhuan, Wang, Weixu, Zhou, Congjin, Ni, Ting, Zheng, Ke. 2023. Single-cell RNA-seq uncovers dynamic processes orchestrated by RNA-binding protein DDX43 in chromatin remodeling during spermiogenesis. In Nature communications, 14, 2499. doi:10.1038/s41467-023-38199-w. https://pubmed.ncbi.nlm.nih.gov/37120627/

2. Dunn, Henry A, Zucca, Stefano, Dao, Maria, Orlandi, Cesare, Martemyanov, Kirill A. 2019. ELFN2 is a postsynaptic cell adhesion molecule with essential roles in controlling group III mGluRs in the brain and neuropsychiatric behavior. In Molecular psychiatry, 24, 1902-1919. doi:10.1038/s41380-019-0512-3. https://pubmed.ncbi.nlm.nih.gov/31485013/

3. Liu, Changhong, Fu, Haijuan, Liu, Xiaoping, Li, Guiyuan, Wu, Minghua. 2018. LINC00470 Coordinates the Epigenetic Regulation of ELFN2 to Distract GBM Cell Autophagy. In Molecular therapy : the journal of the American Society of Gene Therapy, 26, 2267-2281. doi:10.1016/j.ymthe.2018.06.019. https://pubmed.ncbi.nlm.nih.gov/30037656/

4. Zhang, Yi Qiang, Zhang, Jing Jing, Song, Hong Jie, Li, Da Wei. 2017. Overexpression of CST4 promotes gastric cancer aggressiveness by activating the ELFN2 signaling pathway. In American journal of cancer research, 7, 2290-2304. doi:. https://pubmed.ncbi.nlm.nih.gov/29218251/