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This lecture delves into the intricate world of G protein-coupled receptors (GPCRs), focusing on their structure, activation, and signalling pathways. Starting with an overview of GPCR structure and activation mechanisms, the lecture explores the diversity of signalling pathways and the impact of ligands on receptor conformation. It discusses the role of G proteins and arrestins in propagating signals and the implications of biased ligands on cellular responses. The lecture also covers the internalization of GPCRs and their activity within the cell, shedding light on the dynamic nature of receptor signalling. Through various experiments and case studies, the lecture highlights the complexity and adaptability of GPCR signalling.