Adgrl2, also known as latrophilin-2 (Lphn2), CIRL-2, or CL2, is an adhesion G-protein-coupled receptor. It is involved in multiple biological functions, including endothelial barrier function, brain circuit connectivity, equilibrioception, and fluid shear stress mechanotransduction in endothelial cells. It is associated with pathways like eNOS activity regulation, antioxidative responses, and G-protein-mediated signaling, and is of great biological importance in various physiological processes [1,2,3,4,5]. Genetic models, such as knockout mouse models, are valuable for studying its functions.

In a Lphn2 conditional knockout mouse model, deletion of MEC Lphn2 expression selectively impaired retrograde viral labeling of inputs from the ipsilateral presubiculum, revealing its essential role in parahippocampal MEC-PrS circuit connectivity [3]. Loss of Lphn2 specifically in hair cells of mice impaired both balance behavior and the mechanoelectrical transduction (MET) response, and reintroducing it restored vestibular function and MET response, indicating its importance in equilibrioception [4]. Endothelial-specific knockout of latrophilin-2 in mice demonstrated its role in flow-dependent artery remodeling [5].

In conclusion, Adgrl2 is crucial for maintaining normal physiological functions. Studies using KO/CKO mouse models have revealed its role in brain circuit formation, balance sensing, and vascular development and remodeling. Understanding Adgrl2's functions through these models may contribute to exploring its implications in related diseases such as cardiovascular diseases and neurological disorders [3,4,5].