Protease-activated receptors act as a liaison between metabolism and inflammation.

Protease-activated receptors (PARs) constitute a unique subfamily of G protein-coupled receptors comprising four members, PAR1-PAR4. PAR, which govern a broad spectrum of physiological and pathological processes. This review provides a comprehensive synthesis of the roles of PARs in mediating both metabolic dysfunction and inflammatory responses, exploring their potential as dual-function therapeutic targets. We analyze the current literature regarding PAR activation mechanisms and downstream signaling pathways, with a specific focus on their involvement in metabolic syndrome and inflammatory diseases. By evaluating experimental data from genetic ablation and pharmacological inhibition models, we demonstrate that while PAR activation often drives disease progression, targeted inhibition can successfully alleviate symptoms and delay pathogenesis. Ultimately, this review underscores the critical role of PARs in bridging metabolic and inflammatory crosstalk, suggesting that modulating these receptors offers a promising strategy for dual regulation of systemic homeostasis.