CALCRL (calcitonin receptor-like receptor) encodes a G protein-coupled receptor whose ligand specificity is determined by its association with receptor activity-modifying proteins (RAMPs) 1. When complexed with RAMP1, CALCRL forms the CGRP receptor that preferentially binds calcitonin gene-related peptide, while CALCRL-RAMP2/3 complexes serve as adrenomedullin receptors 1. The receptor activates cAMP-dependent signaling pathways upon ligand binding. CALCRL plays crucial roles in cardiovascular regulation, with genetic studies showing that mice lacking RAMP components exhibit altered blood pressure responses to adrenomedullin and CGRP 1. The receptor mediates tissue-protective responses, particularly through adrenomedullin 2 signaling that promotes group 2 innate lymphoid cell functions and limits intestinal inflammation 2. In bone healing, CALCRL is essential for magnesium-induced osteogenesis through CGRP-mediated pathways 3. Disease associations include primary open-angle glaucoma, where CALCRL expression shows protective effects 4, and acute myeloid leukemia, where CALCRL upregulation contributes to therapy resistance 5. The receptor also plays roles in non-small cell lung cancer progression through miRNA regulatory networks 6.