Cell surface protein cross-linking, coimmmunoprecipitation, and confocal microscopy identified CRLR/RAMP1-, CRLR/RAMP2-, and calcitonin receptor isotype 2 (CTR2)/RAMP1 heterodimers as CGRP-, AM-, and CGRP/amylin receptors, linked to cAMP production. Along these lines, effects of structural alterations in the N-terminal extracellular domain of the human CRLR on cell surface expression as well as the association with RAMP and CGRP or AM have been investigated.