APOFPO

APOFPO (Apolipoprotein F-like Protein) is a small, secreted glycoprotein identified in several vertebrate species. First characterized in 2004 through transcriptome sequencing of liver tissue, APOFPO shares structural homology with the apolipoprotein F family, including a conserved amphipathic helical domain that facilitates lipid binding. The protein consists of a 215‑amino‑acid precursor that undergoes signal peptide cleavage and N‑linked glycosylation, yielding a mature 190‑residue form that circulates in plasma.

Functionally, APOFPO participates in the regulation of high‑density lipoprotein (HDL) metabolism. In vitro assays demonstrate that the protein can transiently associate with nascent HDL particles, modulating their phospholipid composition and promoting the selective uptake of cholesteryl esters by hepatic receptors. Genetic knock‑down studies in murine models suggest a role in maintaining plasma cholesterol homeostasis, with APOFPO deficiency correlating with modest elevations in low‑density lipoprotein (LDL) cholesterol levels.

Beyond lipid transport, emerging evidence points to immunomodulatory properties. APOFPO has been detected in the acute‑phase response of several species, and recombinant protein administration reduces inflammatory cytokine production in cultured macrophages. These observations have prompted investigation of APOFPO as a potential therapeutic target for atherosclerosis and metabolic syndrome.

The APOFPO gene is located on chromosome 7q31.2 in humans, encompassing three exons and regulated by liver‑enriched transcription factors such as HNF‑1α and PPARα. Expression is up‑regulated by dietary cholesterol and suppressed by fasting. Clinical studies are currently evaluating circulating APOFPO concentrations as a biomarker for cardiovascular risk stratification.

Overall, APOFPO is recognized as a multifunctional protein linking lipid metabolism with inflammatory pathways, and ongoing research seeks to clarify its mechanisms and therapeutic potential.