RAMPs: the past, present and future

The discovery of receptor-activity-modifying proteins (RAMPs) as accessory proteins required for the appropriate localization and function of certain G-protein coupled receptors (GPCRs) produced a paradigm shift in our understanding of GPCR regulation. Three RAMPs have now been demonstrated to be crucial for various aspects of the life cycle of calcitonin-like receptor (CLR) including endoplasmic reticulum-to-Golgi translocation, internalization and recycling. Although the RAMP–CLR interaction was the first to be identified, other GPCRs belonging to both the class B and C families of GPCRs also seem to be regulated by RAMPs. The recent advances in our knowledge of the cellular and biochemical regulation of RAMPs and how they in turn regulate the life cycle of GPCRs could lead to therapeutic advances in several diseases.