G protein-coupled receptors (GPCRs) represent one of the most abundant protein families encoded by the human genome. They are involved in the modulation of numerous physiological functions and represent major drug targets. Their activity is tightly controlled by a vast array of interacting partners that modulate their membrane targeting, intracellular trafficking and signalling properties. Among them, several proteins from the same family, G protein-coupled receptor associated sorting proteins (GASP), have been shown to display a broad spectrum of interactions with GPCRs. In addition to their postulated role in the modulation of the post-endocytic sorting of these receptors, recent data indicate that several GASPs may modulate the transcriptional activity of the cell through their interaction with transcription factors. However, no clear molecular function has been assigned yet to this protein family. In this review, we describe the discovery of GASPs, their major features, interacting partners, functions and possible involvement in pathological situations including neurodegenerative diseases and cancer.
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