Adgrl2, also known as latrophilin-2 (Lphn2) or CIRL-2, belongs to the adhesion G-protein-coupled receptor family. It plays crucial roles in multiple biological processes, including endothelial function, neuronal circuit connectivity, and mechanotransduction. In endothelial cells, it is involved in pathways related to endothelial barrier function and fluid shear stress mechanotransduction, which are important for vascular development, function, and disease [1,4,5]. In the nervous system, it contributes to the assembly of brain circuits by mediating cell-cell recognition [2].

In conditional knockout mouse models, deletion of MEC Lphn2 expression selectively impairs retrograde viral labeling of inputs arising from the ipsilateral PrS, revealing its essential role in MEC-PrS circuit connectivity [2]. In endothelial-specific knockout mice, latrophilin-2 plays a role in flow-dependent artery remodeling [4,5]. In hair-cell-specific Lphn2-knockout mice, loss of LPHN2 impairs both balance behavior and the mechanoelectrical transduction (MET) response, indicating its role in equilibrioception [3]. In constitutive Adgrl2-/-mice, embryonic lethality is observed, and in Adgrl2 + /-mice, MRI studies reveal microcephaly and vermis hypoplasia [6].

In summary, Adgrl2 is essential for various biological functions, such as maintaining endothelial integrity, neuronal circuit formation, and balance sensing. Studies using Adgrl2 knockout mouse models have provided insights into its role in diseases like cardiovascular diseases and conditions related to microcephaly and rhombencephalosynapsis [4,5,6]. These models have been crucial in uncovering the gene's functions in specific biological processes and disease-related pathways.

References:

1. Jakobs, Philipp, Rafflenbeul, Anne, Post, Willem Berend, Prömel, Simone, Haendeler, Judith. 2024. The Adhesion GPCR ADGRL2/LPHN2 Can Protect Against Cellular and Organismal Dysfunction. In Cells, 13, . doi:10.3390/cells13221826. https://pubmed.ncbi.nlm.nih.gov/39594576/

2. Donohue, Jordan D, Amidon, Ryan F, Murphy, Thomas R, Ajayi, Moyinoluwa T, Anderson, Garret R. . Parahippocampal latrophilin-2 (ADGRL2) expression controls topographical presubiculum to entorhinal cortex circuit connectivity. In Cell reports, 37, 110031. doi:10.1016/j.celrep.2021.110031. https://pubmed.ncbi.nlm.nih.gov/34818557/

3. Yang, Zhao, Zhou, Shu-Hua, Zhang, Qi-Yue, Yu, Xiao, Sun, Jin-Peng. 2025. A force-sensitive adhesion GPCR is required for equilibrioception. In Cell research, 35, 243-264. doi:10.1038/s41422-025-01075-x. https://pubmed.ncbi.nlm.nih.gov/39966628/

4. Tanaka, Keiichiro, Chen, Minghao, Prendergast, Andrew, Nicoli, Stefania, Schwartz, Martin A. 2024. Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions. In The EMBO journal, 43, 3175-3191. doi:10.1038/s44318-024-00142-0. https://pubmed.ncbi.nlm.nih.gov/38886581/

5. Tanaka, Keiichiro, Chen, Minghao, Prendergast, Andrew, Nicoli, Stefania, Schwartz, Martin A. 2024. Latrophilin-2 mediates fluid shear stress mechanotransduction at endothelial junctions. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.06.13.598386. https://pubmed.ncbi.nlm.nih.gov/38915515/

6. Vezain, Myriam, Lecuyer, Matthieu, Rubio, Marina, Laquerrière, Annie, Saugier-Veber, Pascale. 2018. A de novo variant in ADGRL2 suggests a novel mechanism underlying the previously undescribed association of extreme microcephaly with severely reduced sulcation and rhombencephalosynapsis. In Acta neuropathologica communications, 6, 109. doi:10.1186/s40478-018-0610-5. https://pubmed.ncbi.nlm.nih.gov/30340542/