GPCR signaling from a primary cilium perspective

) signaling, enabling integration and hierarchical control of multiple GPCR inputs. Finally, we examine the physiological consequences of ciliary GPCR signaling in neural, renal, adipose, and pancreatic and developmental tissues, where defects in ciliary signaling contribute to metabolic disease, impaired morphogenesis, and tissue homeostasis, and ciliopathies-a range of human disorders arising from primary cilium dysfunction. Together, these studies establish the primary cilium as a dynamic and modular GPCR signaling hub and underscore the importance of subcellular localization in determining receptor function and signaling specificity. SIGNIFICANCE STATEMENT: Beyond their traditional role at the plasma membrane, many GPCRs signal from primary cilia, specialized cellular compartments that create unique signaling environments. This review synthesizes advances in ciliary GPCR trafficking, organization, and signal transduction, showing how subcellular localization determines receptor function and how disrupted ciliary signaling contributes to human diseases, including ciliopathies, metabolic disorders, and developmental defects.