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

PAQR11, an evolutionarily conserved seven-transmembrane receptor localized at the Golgi apparatus, functions as a master coordinator of metabolic-immune integration across physiological systems. This review synthesizes cutting-edge evidence revealing how its unique subcellular positioning enables compartmentalized regulation of Ras signaling and inflammasome activation through allosteric conformational switching, thereby governing immunometabolic adaptations from Caenorhabditis elegans 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.