The serum amyloid A (SAA) family comprises apolipoproteins that are differentially expressed in response to inflammation. Acute-phase SAA (A-SAA) is a major vertebrate acute-phase reactant, with concentrations increasing by up to 1000-fold during inflammation. A-SAA mRNAs and proteins have been identified in all vertebrates studied, while constitutive SAA (C-SAAs) are minimally induced and found only in human and mouse. The liver is the primary site of A-SAA synthesis, but extrahepatic production has been reported in various species. In vitro, A-SAA mRNA induction is driven by cytokine signaling pathways, particularly those of interleukin-1 and interleukin-6, and can be enhanced by glucocorticoids. Transcription factors such as NF-κB, C/EBP, YY1, AP-2, SAF, and Sp1 are involved in defining cytokine responsiveness and cell specificity. A-SAA is post-transcriptionally regulated and has potential roles in lipid metabolism, extracellular matrix degradation, and inflammatory cell recruitment. It is implicated in the pathogenesis of chronic inflammatory diseases, including amyloidosis, atherosclerosis, and rheumatoid arthritis. The acute-phase response involves the induction of inflammatory mediators and biosynthetic changes, particularly in the liver, to counteract tissue injury, infection, and trauma. The SAA family members, including A-SAA and C-SAAs, play crucial roles in this process, with A-SAA being the archetypal vertebrate major acute-phase protein. The structure and function of A-SAA proteins, as well as their induction and regulation, are discussed in detail.The serum amyloid A (SAA) family comprises apolipoproteins that are differentially expressed in response to inflammation. Acute-phase SAA (A-SAA) is a major vertebrate acute-phase reactant, with concentrations increasing by up to 1000-fold during inflammation. A-SAA mRNAs and proteins have been identified in all vertebrates studied, while constitutive SAA (C-SAAs) are minimally induced and found only in human and mouse. The liver is the primary site of A-SAA synthesis, but extrahepatic production has been reported in various species. In vitro, A-SAA mRNA induction is driven by cytokine signaling pathways, particularly those of interleukin-1 and interleukin-6, and can be enhanced by glucocorticoids. Transcription factors such as NF-κB, C/EBP, YY1, AP-2, SAF, and Sp1 are involved in defining cytokine responsiveness and cell specificity. A-SAA is post-transcriptionally regulated and has potential roles in lipid metabolism, extracellular matrix degradation, and inflammatory cell recruitment. It is implicated in the pathogenesis of chronic inflammatory diseases, including amyloidosis, atherosclerosis, and rheumatoid arthritis. The acute-phase response involves the induction of inflammatory mediators and biosynthetic changes, particularly in the liver, to counteract tissue injury, infection, and trauma. The SAA family members, including A-SAA and C-SAAs, play crucial roles in this process, with A-SAA being the archetypal vertebrate major acute-phase protein. The structure and function of A-SAA proteins, as well as their induction and regulation, are discussed in detail.