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This lecture covers the basics of G protein-coupled receptors (GPCRs), including their classical signaling scheme, shut down mechanisms, diversity, complexity, and testing of signaling pathways. It also delves into the structures of GPCRs, their historical background, and recent advancements in biochemistry and pharmacology. The lecture explores the three families of GPCRs based on primary sequences and ligand binding sites, the GPCR cycle involving ligand-induced GDP-GTP exchange, and GTP hydrolysis. Additionally, it discusses the significance of GPCRs as drug targets, the success of Heptares in GPCR research, and the regulation of G-protein signaling by RGS proteins.