ADGRL2 (latrophilin-2) is an adhesion G protein-coupled receptor that functions as a mechanosensor and cell-adhesion mediator with diverse physiological roles 1. In the nervous system, ADGRL2 localizes to postsynaptic spines of excitatory synapses and mediates synapse specificity by interacting with presynaptic teneurins to promote synapse formation 1. Beyond synaptic function, ADGRL2 serves as a force-sensitive mechanoreceptor: it is essential for equilibrioception in vestibular hair cells, where it converts mechanical force stimuli into increased channel opening of TMC1, enabling mechanotransduction and balance maintenance 2. In endothelial cells, ADGRL2 mediates fluid shear stress mechanotransduction at cell-cell junctions, activating Gαi2 and Gαq/11 signaling upstream of the PECAM-1 complex to regulate flow-dependent angiogenesis and artery remodeling; human genetic variants in ADGRL2 correlate with cardiovascular disease 3. ADGRL2 also provides cytoprotection against septic endothelial dysfunction by preserving eNOS activity and enhancing antioxidative NRF2 responses 4. In epithelial tissues, ADGRL2 specifically activates Gα13 to enable epidermal differentiation 5. In cancer, ADGRL2 polymorphisms associate with severe malaria risk 6, and ADGRL2 promotes breast cancer cell migration, adhesion, and invasion through ROCK and PKA signaling 7. These findings establish ADGRL2 as a multifunctional mechanoreceptor critical for neuronal, vascular, and epithelial homeostasis.