Myeloid-related protein 14 (MRP14 (also known as S100A9))

Myeloid-related protein 14 (MRP14), also known as S100A9, is a cytosolic calcium-binding protein highly expressed in neutrophils and monocytes, where it often forms a heterodimer known as calprotectin with its partner MRP8 (S100A8). MRP14 plays a critical regulatory role in innate immune responses, coordinating cellular signals via calcium binding, modulating cytoskeletal reorganization, and integrating MAP kinase pathways to influence the migration and activation of phagocytes (e.g., neutrophil transendothelial migration, microtubule dynamics). Extracellularly, the MRP8/14 complex can signal via receptors like TLR-4, RAGE, and CD36, linking innate immune activation with inflammation, tissue injury, and repair, particularly in vascular contexts. MRP8/14 is secreted by activated myeloid cells through a tubulin-dependent, non-classical secretion pathway. Elevated levels of MRP8/14 in blood and tissue serve as biomarkers for inflammatory and autoimmune diseases and are linked with worse outcomes in diseases like atherosclerosis, arthritis, infection, and cancer. The molecule is an emerging therapeutic target for modulation of inflammatory and immune-mediated diseases due to its central role in the pathogenesis and persistence of inflammation.

Other names

S100A9Calgranulin BCalprotectin (as the S100A8/S100A9 complex)MRP-14LCN9p14

As a target, modulation of MRP14 (S100A9) or its complex with MRP8 (S100A8) can influence inflammation via effects on immune cell recruitment, cytokine signaling, and calcium-dependent and MAP kinase-dependent pathways. Targeting MRP8/14 may dampen inflammatory responses and therefore has therapeutic interest in diseases like atherosclerosis and autoimmune disorders.