G protein-coupled receptors (GPCRs) are a large family of proteins with diverse functions. Several GPCR interacting proteins, including other membrane-spanning proteins, have now been identified. They have diverse roles and frequently assist GPCR translocation to the cell surface. Receptor activity-modifying proteins (RAMPs) are examples of such proteins. RAMPs interact with several GPCRs but their best studied functions are with the calcitonin receptor-like receptor (CLR) and calcitonin receptor (CTR), where the consequences of RAMP interaction include affecting receptor trafficking both to and from the cell surface, receptor pharmacology and cellular signalling. RAMP1 also participates in the binding of small molecule drugs to the CGRP receptor (CLR + RAMP1), a target for the treatment of migraine.