Arrestins come of age: a personal historical perspective

Visual arrestin and the two β-arrestins (1 and 2) were originally discovered 25-30 years ago in the context of their ability to desensitize phosphorylated G protein-coupled receptors (rhodopsin and the β2-adrenergic receptor, respectively). A fourth retinal-specific member of the family (X-arrestin) was discovered later. Over the past 10-15 years, however, it has become clear that these versatile molecules subserve a host of other roles in modulating and mediating the function of most GPCRs as well as other types of receptors. Functioning as multifunctional adaptor proteins, the β-arrestins also play prominent roles in receptor endocytosis, signaling, trafficking, and ubiquitination among others. Here, I provide a brief personal perspective on how the field has evolved since its inception and speculate on future directions.