ADGRF4 (GPR115), an adhesion G protein-coupled receptor, is an orphan receptor belonging to the ADGRF subfamily 1. While its endogenous ligand remains unknown, ADGRF4 functions as a G protein-coupled receptor capable of adenylate cyclase-activating signaling 1. ADGRF4 demonstrates tissue-specific expression, particularly enriched in skin and tooth tissues. In tooth development, ADGRF4 plays a critical role in enamel mineralization by regulating carbonic anhydrase 6 (CAR6) expression in mature ameloblasts, with ADGRF4 knockout mice exhibiting hypomineralized enamel due to dysregulated ion transport and pH homeostasis 2. In skin, ADGRF4 localizes intracellularly along keratin filaments and is essential for epidermal differentiation and KRT1/10 expression; its deletion impairs keratinocyte stratification 3. Clinically, ADGRF4 overexpression correlates with poor prognosis across multiple cancers. High ADGRF4 expression is associated with shortened overall and recurrence-free survival in breast cancer patients and worse outcomes in uterine endometrial carcinoma 45. In lung cancer, ADGRF4 regulates cell invasiveness through PPP2C signaling 6. These findings identify ADGRF4 as a potential immunotherapeutic target and prognostic biomarker in cancer while highlighting its physiologic importance in tissue differentiation and mineralization.