PAQR11: An evolutionarily conserved Golgi receptor governing metabolic-immune crosstalk and systemic homeostasis.

to mammals. Pathophysiologically, PAQR11 disruption precipitates multisystem disorders: impaired insulin sensitivity and adipokine signaling exacerbate obesity-associated lipotoxicity; enhanced NLRP3 activation via Ras scaffolding drives autoimmune pathogenesis; and rewired fatty acid oxidation coordinates tumor-stromal crosstalk in obesity-related malignancies. Mechanistically, PAQR11 operates as a spatiotemporal organizer by assembling signaling hubs at the Golgi membrane-its 7TM domain acting as a ligand-gated switch for signal bias-while emerging roles in circadian immunometabolism highlight broader implications for systemic homeostasis. Future research must resolve tissue-specific receptor interactomes and exploit cross-species conservation for targeted physiological modulation, bridging molecular architecture with organismal pathophysiology.