ADGRG1 is an adhesion G protein-coupled receptor that functions as a molecular sensor and regulator of cell-cell interactions and tissue homeostasis. As a primary function, ADGRG1 binds the steroid hormone 17α-hydroxypregnenolone (17-OH PREG), triggering conformational changes that activate G(12/13) protein signaling and downstream RhoA pathway activation 1. This ligand-binding mechanism enables multiple physiological roles: ADGRG1 promotes cell adhesion through interactions with collagen III and TGM2, mediates hemostatic responses to shear force in platelets, and suppresses angiogenesis by inhibiting VEGFA production 2345. Crucially, ADGRG1 functions as a potent ferroptosis suppressor; 17-OH PREG-mediated signaling downregulates CD36 to alleviate ferroptosis-induced liver injury 1. In the nervous system, ADGRG1 regulates cortical development and lamination by inhibiting neuronal migration via RhoA activation, maintains myelination through TGM2 interaction, and drives protective microglial responses in Alzheimer's disease by activating MYC-dependent homeostatic and phagocytic programs 67. Disease relevance includes cortical dysplasia (bilateral frontoparietal and perisylvian types) and emerging evidence suggests roles in cancer and autoimmune disease. ADGRG1 marks functionally distinct T cell subsets in rheumatoid arthritis and gastrointestinal cancers, and appears enriched in cytotoxic CD8+ T cells associated with leukemia remission post-transplantation 8910. Its dual tumor-suppressive and tumor-promoting functions highlight context-dependent disease associations 11.