Calcitonin receptor-like receptor (CALCRL)

Calcitonin receptor-like receptor (CALCRL) is a class B G protein-coupled receptor that requires association with one of three receptor activity-modifying proteins (RAMP1, RAMP2, or RAMP3) to form a functional receptor complex[1][3]. The pairing with RAMP1 yields a high-affinity receptor for calcitonin gene-related peptide (CGRP), crucial for mediation of potent vasodilation, modulation of nociceptive (pain) signaling, and implicated in migraine and neurogenic inflammation. Pairing with RAMP2 or RAMP3 creates adrenomedullin (AM) or mixed CGRP/AM receptors central to vascular tone regulation, angiogenesis, and endothelial integrity[1][2][3]. CALCRL is broadly expressed in vascular and lymphatic endothelium, nervous system, and fetal tissues. Pharmacologically, antagonists targeting this receptor complex (notably in conjunction with RAMP1) form the current mainstay of CGRP-migraine therapy[2]. Genetic ablation in animal models causes severe developmental defects, underscoring its essential roles in cardiovascular and lymphatic homeostasis[1]. The receptor is also thought to participate in anti-inflammatory signaling, vascular integrity, and anti-nociceptive pathways[1][2][3].

Other names

Calcitonin gene-related peptide type 1 receptorCGRP type 1 receptorCRLRCGRPRLMPHM8calcitonin receptor-likecalcitonin receptor-like protein

Antagonism/blockade of calcitonin gene-related peptide (CGRP) receptor to prevent vasodilation and modulation of migraine pain signaling [e.g., erenumab] Inhibition of CGRP binding to the receptor Modulation of G protein signaling (Gs, Gi, Gq)