G-protein-coupled receptors (GPCRs) are the largest and most versatile family of signaling receptors in humans. They respond to diverse external signals, such as photons, proteins, peptides, chemicals, hormones, lipids, and sugars, and mediate a myriad of functions in the human body. Signaling through GPCRs can be optimized by enriching receptors and downstream effectors in discrete cellular domains. Many GPCRs have been found to be selectively targeted to cilia on numerous mammalian cell types. Moreover, investigations into the pathophysiology of human ciliopathies have implicated GPCR ciliary signaling in a number of developmental and cellular pathways. Thus, cilia are now appreciated as an increasingly important nexus for GPCR signaling. Yet, we are just beginning to understand the precise signaling pathways mediated by most ciliary GPCRs and how they impact cellular function and mammalian physiology.
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