UTS2R encodes a G protein-coupled receptor that binds urotensin-2 and urotensin-2B peptides 1. Upon ligand binding, UTS2R activates intracellular signaling through Gq/11 coupling, leading to phospholipase C activation and increased intracellular calcium 1. The receptor also activates MAPK/ERK pathways via Gi/Go coupling 1. UTS2R plays critical roles in cardiovascular function, with urotensin-II demonstrating potent vasoconstrictive effects that may exceed endothelin-1, making it potentially the most potent mammalian vasoconstrictor 2. The receptor system contributes to cardiovascular homeostasis and may be involved in cardiovascular pathologies 2. Recent studies reveal UTS2R's involvement in subarachnoid hemorrhage pathophysiology, where it mediates early meningeal responses and delayed macrophage-dependent vasospasm leading to cognitive dysfunction 3. Clinically, UTS2R has emerged as a therapeutic target, with receptor antagonists showing potential for treating subarachnoid hemorrhage complications 3. Additionally, UTS2R demonstrates unexpected off-target effects, as remdesivir acts as a partial agonist causing cardiomyocyte dysfunction through Gαi/o-dependent AKT/ERK signaling 4. The receptor also functions in tissue homeostasis, with UTS2R-expressing progenitor cells playing essential roles in intervertebral disc maintenance 5.