SAA4 (serum amyloid A4, constitutive) encodes a constitutively expressed apolipoprotein that functions as a minor component of high-density lipoproteins (HDL) under homeostatic conditions. SAA4 is synthesized exclusively in the liver during homeostasis and maintains plasma concentrations of approximately 55 ± 13 μg/ml in healthy individuals 1. Unlike acute-phase SAA proteins (SAA1/SAA2), SAA4 represents more than 90% of total SAA during non-inflammatory states and associates with a specific subpopulation of HDL particles, as well as very low-density lipoproteins (VLDL), but is absent from low-density lipoproteins 1. The protein contains an eight amino acid insertion relative to other human SAA proteins and exhibits distinct structural features including modified lipid binding domains and unique secondary structure elements 2. SAA4 expression can be induced in human monocytes and macrophages under specific inflammatory conditions (LPS/dexamethasone treatment), though this differs markedly from classical pro-inflammatory cytokine responses 3. Clinically, decreased SAA4 expression is associated with hepatocellular carcinoma progression and poor prognosis, suggesting potential utility as a diagnostic biomarker 4. Additionally, SAA4 levels are modulated by metformin treatment and may serve as a biomarker for therapeutic response in rheumatoid arthritis 56.