ADGRG4 (adhesion G protein-coupled receptor G4) is an orphan adhesion GPCR that functions as a Gs-coupled receptor activating adenylate cyclase signaling 1. The receptor undergoes autoproteolysis to generate α and β subunits, with the β subunit's 'Stachel sequence' acting as a tethered agonist that inserts into the seven-transmembrane bundle to activate downstream signaling 1. ADGRG4 possesses a conserved N-terminal pentraxin-like domain that forms Ca²⁺-independent homodimers, suggesting a role in sensing mechanical forces, particularly in intestinal enterochromaffin and Paneth cells 2. Functionally important motifs resemble those of class A and class B GPCRs alongside unique adhesion GPCR-specific elements 3. Disease relevance includes cancer development: ADGRG4 variants show associations with ovarian cancer risk in specific populations 4, and high ADGRG4 expression correlates with poor overall survival in breast cancer 5. Additionally, ADGRG4 variants were identified in familial mandibular micrognathism with X-linked inheritance patterns 6. These findings suggest ADGRG4 participates in cell adhesion, migration, and immune modulation relevant to oncogenesis.