FAM3D (FAM3 metabolism regulating signaling molecule D) is a secreted cytokine-like protein that functions as a pleiotropic regulator of metabolic and immune processes. Mechanistically, FAM3D exerts its effects primarily through activation of formyl peptide receptors (FPR1 and FPR2) 12. In hepatocytes, the FAM3D-FPR1 axis activates the hnRNP U-GR-SCAD pathway to enhance lipid oxidation and suppress gluconeogenesis, while hepatic FAM3D overexpression ameliorates hyperglycemia and steatosis in obese mice 2. Conversely, FAM3D impairs endothelial function by causing eNOS uncoupling through FPR1/FPR2-mediated oxidative stress, exacerbating angiotensin II-induced hypertension, and targeting endothelial FAM3D ameliorates hypertension in multiple models 1. Disease relevance is evident across multiple conditions: elevated FAM3D associates with hypertension risk 1, FAM3D is identified as a potential therapeutic target for type 2 diabetes 3, and elevated circulating FAM3D increases gastric cancer susceptibility 4. In contrast, low FAM3D expression correlates with worse prognosis in head and neck squamous cell carcinoma through epithelial-mesenchymal transition regulation 5 and colorectal cancer through ATF4-SESN2-mTORC1 pathway activation 6. These context-dependent effects suggest FAM3D as a promising therapeutic target across cardiometabolic and malignant diseases.