Insight into the regulatory mechanism of β-arrestin2 and its emerging role in diseases

beta-arrestin2, a member of the arrestin family, mediates the desensitization and internalization of most G protein-coupled receptors (GPCRs) and functions as a scaffold protein in signalling pathways. Previous studies have demonstrated that beta-arrestin2 expression is dysregulated in malignant tumours, fibrotic diseases, cardiovascular diseases and metabolic diseases, suggesting its pathological roles. Transcription and post-transcriptional modifications can affect the expression of beta-arrestin2. Furthermore, post-translational modifications, such as phosphorylation, ubiquitination, SUMOylation and S-nitrosylation affect the cellular localization of beta-arrestin2 and its interaction with downstream signalling molecules, which further regulate the activity of beta-arrestin2. This review summarizes the structure and function of beta-arrestin2 and reveals the mechanisms involved in the regulation of beta-arrestin2 at multiple levels. Additionally, recent studies on the role of beta-arrestin2 in some major diseases and its therapeutic prospects have been discussed to provide a reference for the development of drugs targeting beta-arrestin2.