Pathophysiological impact of the adhesion G protein-coupled receptor family

G protein-coupled receptors (GPCRs) represent one of the most targeted drug classes in the human genome, accounting for greater than 40% of all Food and Drug Administration-approved drugs. However, the second-largest family of GPCRs, known as adhesion GPCRs (aGPCR), have yet to serve as a clinical target despite increasing evidence of their physiological and pathological functions, which suggests an opportunity toward the development of novel therapeutics. To date, the pathophysiological function of aGPCRs is associated with a plethora of diseases including cancer, central nervous system disorders, immunity and inflammation, and others. To highlight their potential as pharmacological targets, we will review three distinct aGPCR members (ADGRG1, ADGRE5, and ADGRF5), highlighting their molecular mechanisms of action and contributions to the development of pathophysiology.