Serum amyloid A: multifaceted roles in inflammation and cellular interactions

Serum amyloid A (SAA) is a conserved family of acute-phase proteins primarily produced in the liver but also expressed in extrahepatic tissues during inflammation. As a key component of the acute-phase response, SAA exhibits dynamic upregulation, with serum levels rising up to 1000-fold during inflammation, underscoring its significance in immune modulation and disease pathogenesis. This review provides a comprehensive analysis of SAA's structure, origins, and functions, emphasizing its interactions with immune and non-immune cells. SAA influences cellular processes such as cytokine production, leukocyte migration, and receptor activation, linking it to the pathogenesis of inflammation related diseases. Notably, SAA facilitates chronic inflammation, fibrosis, and therapy resistance while also playing protective roles in infection and tissue repair. The review highlights emerging insights into SAA's dual roles as both a biomarker and a therapeutic target. It underscores critical gaps in understanding SAA's context-dependent effects, receptor interactions, and its regulatory mechanisms in diverse inflammatory settings. These findings point to the necessity of further research to harness SAA's diagnostic and therapeutic potential, particularly in chronic inflammatory and autoimmune diseases. By synthesizing current evidence, this work aims to guide future studies toward advancing clinical interventions targeting SAA-mediated pathways.