ADIPOR2 is a cell surface receptor for adiponectin, an abundant adipocyte-derived hormone central to metabolic homeostasis 1. Upon adiponectin binding, ADIPOR2 activates intracellular signaling cascades that enhance fatty acid oxidation and glucose uptake, primarily through PPARA activation and AMP kinase stimulation 12. ADIPOR2 functions alongside its homolog ADIPOR1 to mediate adiponectin's metabolic effects in liver, muscle, and adipose tissue 1. Beyond glucose-lipid metabolism, ADIPOR2 plays immunomodulatory roles. In macrophages, ADIPOR2 activation promotes anti-inflammatory M2-like polarization, contributing to atherosclerosis prevention 3. Recent mechanistic studies reveal ADIPOR2 activates a Ca²⁺-dependent signaling axis involving CaMKII and NOS3, rapidly inducing nitric oxide production for hepatoprotection in acute liver failure 4. Clinically, ADIPOR2 downregulation is associated with metabolic dysfunction. In obesity, reduced abdominal ADIPOR2 expression contributes to adiponectin resistance and insulin resistance, perpetuating metabolic disease 5. ADIPOR2 levels correlate with disease progression in nonalcoholic steatohepatitis and liver fibrosis 6. Notably, elevated ADIPOR2 expression associates with poor breast cancer prognosis 7. ADIPOR2-targeted therapeutics show promise for metabolic and liver diseases 64.