Receptor Activity-Modifying Proteins (RAMPs): New Insights and Roles

Annu Rev Pharmacol Toxicol. 2016:56:469-87. doi: 10.1146/annurev-pharmtox-010715-103120. Epub 2015 Oct 23.


It is now recognized that G protein-coupled receptors (GPCRs), once considered largely independent functional units, have a far more diverse molecular architecture. Receptor activity-modifying proteins (RAMPs) provide an important example of proteins that interact with GPCRs to modify their function. RAMPs are able to act as pharmacological switches and chaperones, and they can regulate signaling and/or trafficking in a receptor-dependent manner. This review covers recent discoveries in the RAMP field and summarizes the known GPCR partners and functions of RAMPs. We also discuss the first peptide-bound structures of RAMP-GPCR complexes, which give insight into the molecular mechanisms that enable RAMPs to alter the pharmacology and signaling of GPCRs.

Keywords: CGRP; CRF; GPCR; GPR30; RAMP; VIP; adrenomedullin; amylin; calcium-sensing receptor; heterodimer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Membrane Proteins / metabolism
  • Protein Binding / physiology
  • Receptor Activity-Modifying Proteins / metabolism*
  • Receptors, G-Protein-Coupled / metabolism
  • Signal Transduction / physiology


  • Membrane Proteins
  • Receptor Activity-Modifying Proteins
  • Receptors, G-Protein-Coupled