G protein-coupled receptors (GPCRs) are among the most important protein families in sensing environmental changes at the cellular level providing adequate response and adaptation to them. Seminal discoveries elucidated over the last 20 years the basic signaling modules and the structural basis of the signal transmission of GPCRs. Their enormous potential as drug targets has been recognized with 30-40% of currently marketed drugs targeting GPCRs and many others remaining to explored. Emerging evidences highlight the fact that GPCRs are not functioning as isolated entities but are part of a defined microenvironment. This microenvironment is defined by the tissues and cell types in which receptors are expressed, by the localization of receptors in subcellular compartments and membrane microdomains and by the formation of molecular complexes with other receptors. All these parameters have an important impact on receptor function and are essential for their therapeutic applications.

The ambition of the i-GPCRnet is to tackle the largely unexplored question of the impact of the microenvironments on GPCR function and how perturbation of this microenvironment impacts on common diseases such as cancer, metabolic and neurodegenerative diseases as well as their therapies. A better understanding of the GPCR microenvironment holds the promise of unprecedented therapeutic opportunities in terms of tissue specificity and specific pharmacological targeting that will eventually lead to the design of innovative and tailored drugs for precision medicine. To reach this goal the i-GPCRnet consortium will bring together chemists, biophysicists, bioinformaticians, mathematicians, systems and cellular biologists and pharmacologists.