{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nOrosomucoid 1 (ORM1), also known as alpha‐1–acid glycoprotein (AGP), is a highly abundant acute‐phase plasma protein that plays dual roles in pharmacology and immunology. Genetic studies have shown that polymorphisms or haplotypes spanning the ORM1/ORM2 locus are associated with significant variability in drug responses—for example, influencing warfarin dose requirements—while structure–function analyses reveal that ORM1 displays selective, high‐affinity binding for specific stereoisomers of coumarin‐type anticoagulants. These observations underscore its critical function as a drug carrier modulating the pharmacokinetics of various therapeutic agents."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its role in drug binding, ORM1 functions as an important immunomodulator. It can trigger subtle calcium signaling in neutrophils through interaction with receptors such as Siglec‑5, thereby influencing innate immune responses. In monocytes and macrophages, ORM1 upregulates the expression of CD163—a scavenger receptor essential for hemoglobin clearance and reduction of oxidative stress—and promotes the polarization toward an M2b phenotype that, while dampening antibacterial functions, helps control excessive inflammation. Moreover, ORM1 expression is responsive to hormonal cues; for instance, its regulation by the vitamin D receptor couples endocrine signals to the deactivation of pro‐inflammatory macrophages."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "3", "end_ref": "8"}]}, {"type": "t", "text": ""}, {"type": "p", "children": [{"type": "t", "text": "\nStructural and spectroscopic investigations further illuminate ORM1’s versatility as a carrier protein. Crystallographic analyses have demonstrated that a conserved residue (notably Trp25) within its characteristic eight‐stranded β–barrel provides a hydrophobic binding cavity for a diverse array of ligands including polymyxins. This precise molecular recognition mechanism not only underpins its drug‐binding capacity but also highlights how subtle changes in ORM1’s glycoform composition and genetic variants may influence both its pharmacological interactions and its immunomodulatory properties."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}]}]}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Eszter Hazai, Júlia Visy, Ilona Fitos, et al. 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