Research tools such as the SAA1 knockout mice and transgenic mice have become available only recently. It has been well established, however, that elevated plasma concentration of SAA1 is associated with a multitude of inflammatory conditions. As a result, SAA1 has been a clinical indicator and reliable biomarker for inflammatory diseases, chronic metabolic disorders and late-stage malignancy. Inflammatory amyloidosis results from chronic inflammation with increased production of SAA1, which is a major precursor of amyloid A fibril deposit in various tissues. SAA1 has been extensively studied for its binding to HDL, with results suggesting a role in lipid metabolism. During the acute-phase response, elevated levels of SAA1 in the plasma displaces ApoA-I and becomes a major apolipoprotein of HDL. The exact biological consequence of HDL remodeling by SAA1 is still under investigation, using recently developed tools such as the Saa1 and Saa2 knockout mice. SAA1 is also believed to contribute to the development of atherosclerosis. However, in an ApoE-deficient mouse model, deletion of the Saa1/Saa2 genes does not appear to affect atherosclerotic lesions. "Ex vivo" and "in vitro" studies have shown that the recombinant human SAA1 hybrid protein has strong chemotactic activity for neutrophils and macrophages. This effect is believed to be mediated through FPR2, a G protein-coupled chemoattractant receptor. The same receptor also mediates the cytokine-like activity of the recombinant SAA1, resulting in an elevated expression of IL-8 in neutrophils. The recombinant SAA1 has been reported to induce the expression of a variety of inflammatory cytokines including IL-1β, TNF-α, IL-6, IL-12p40, as well as immunoregulatory cytokines such as IL-23, IL-33 and growth-stimulatory cytokines such as G-CSF. SAA1 may also be produced by macrophages and epithelial cells in various tissues. It has been shown to promote local Th17 response in the gut. This finding, which is based on both Saa1/Saa2 knockout mice and "ex vivo" studies of T cells, strongly suggest a local immunomodulatory function of SAA1 as opposed to its established role as an acute-phase protein produced in the liver and present in the plasma as an apolipoprotein of HDL.