Adhesion G Protein-coupled Receptors (AGPCRs)

dhesion G Protein-Coupled Receptors (AGPCRs) are a subfamily of the G protein-coupled receptor (GPCR) superfamily, primarily mediating cell adhesion, cell-cell communication, and signal transduction, playing crucial roles in neural development, immune regulation, angiogenesis, and cancer progression.
The AGPCR family consists of 33 members, categorized based on function into immune-related types (e.g., ADGRE1-5), development and nervous system-related types (e.g., ADGRG1, ADGRL3), and cardiovascular regulatory types (e.g., ADGRA2), all designated with the "ADGR" prefix. A distinctive feature of AGPCRs is their long extracellular N-terminal domain and GPS (G protein-coupled receptor proteolytic site), which enables self-activation via the “Stachel” domain upon external stimulation, facilitating signal transduction.
Dysfunction of AGPCRs is associated with brain developmental disorders, inflammatory diseases, infertility, and various cancers. For instance, mutations in ADGRG1 (GPR56) can cause bilateral frontoparietal polymicrogyria (BFPP), mutations in ADGRE2 are linked to vibratory urticaria, and deficiency of ADGRG2 (GPR64) may result in congenital bilateral absence of the vas deferens (CBAVD). Additionally, GPR56 plays a key role in melanoma metastasis and glioma progression. With advancing research into AGPCR structure and function, this family has become a major focus in the study of neurological disorders, immune diseases, and cancer^[1][2].