ADGRF5 (adhesion G protein-coupled receptor F5) is a multifunctional adhesion GPCR with diverse physiological roles across multiple organ systems 1. In lung tissue, ADGRF5 is essential for surfactant homeostasis in alveolar type II cells, functioning through downstream GNAQ/GNA11 protein activation and cortical F-actin assembly modulation 2. The receptor serves as a key mediator of metabolic homeostasis by functioning as a receptor for soluble FNDC4 (sFNDC4) in white adipose tissue, where it enhances insulin sensitivity and glucose tolerance while reducing local inflammation 3. In skeletal tissue, ADGRF5 plays a crucial role in peri-implant fibrosis, with its inhibition preventing fibrotic tissue formation and promoting bone formation around implants 4. The receptor demonstrates significant clinical relevance in cancer, where it facilitates breast cancer progression by suppressing MMP8-mediated antitumorigenic effects and modulating the tumor microenvironment 5. Additionally, ADGRF5 serves as a diagnostic biomarker for differentiating renal tumor subtypes 6 and shows therapeutic potential in inflammatory conditions, with novel agonists demonstrating anti-inflammatory effects in colitis models 7. The receptor's involvement in acral mesenchymal tumors through THBS1::ADGRF5 fusions further highlights its pathological significance 8.