Prostaglandin E (PGE) receptors are G-protein-coupled receptors (GPCRs) that respond to PGE2. There are four subtypes, EP1, EP2, EP3, and EP4, with multiple isoforms of EP3. These receptors differ in signal transduction, tissue localization, and expression regulation. Knockout mice studies have clarified the roles of each subtype in physiological and pathophysiological processes. Recent research has identified the molecular and biochemical diversity of PGE receptors, revealing their involvement in various biological functions. EP1, EP2, EP3, and EP4 have distinct signal transduction properties, with EP1 mediating Ca²+ channel gating, EP2 and EP4 increasing cAMP levels, and EP3 inhibiting adenylate cyclase via Gi. EP3 also has multiple splice variants with different signal transduction properties. The distribution of these receptors varies among tissues, with EP3 and EP4 being widely expressed, while EP1 is restricted to certain organs. Expression of EP receptors is regulated by physiological and pathophysiological stimuli, such as lipopolysaccharide in macrophages. In reproductive organs, EP receptors are expressed in specific cell types and are regulated by hormones. EP subtypes mediate various physiological functions, including inflammation, pain, and immune responses. The development of subtype-specific agonists and antagonists has enabled the study of PGE2-mediated processes. Overall, the identification of PGE receptors has provided insights into their diverse roles in health and disease.Prostaglandin E (PGE) receptors are G-protein-coupled receptors (GPCRs) that respond to PGE2. There are four subtypes, EP1, EP2, EP3, and EP4, with multiple isoforms of EP3. These receptors differ in signal transduction, tissue localization, and expression regulation. Knockout mice studies have clarified the roles of each subtype in physiological and pathophysiological processes. Recent research has identified the molecular and biochemical diversity of PGE receptors, revealing their involvement in various biological functions. EP1, EP2, EP3, and EP4 have distinct signal transduction properties, with EP1 mediating Ca²+ channel gating, EP2 and EP4 increasing cAMP levels, and EP3 inhibiting adenylate cyclase via Gi. EP3 also has multiple splice variants with different signal transduction properties. The distribution of these receptors varies among tissues, with EP3 and EP4 being widely expressed, while EP1 is restricted to certain organs. Expression of EP receptors is regulated by physiological and pathophysiological stimuli, such as lipopolysaccharide in macrophages. In reproductive organs, EP receptors are expressed in specific cell types and are regulated by hormones. EP subtypes mediate various physiological functions, including inflammation, pain, and immune responses. The development of subtype-specific agonists and antagonists has enabled the study of PGE2-mediated processes. Overall, the identification of PGE receptors has provided insights into their diverse roles in health and disease.