Macrophage migration inhibitory factor assembles into a trimer composed of three identical subunits. Each of these monomers contain two antiparallel alpha helices and a four-stranded beta sheet. The monomers surround a central channel with 3-fold rotational symmetry.^[6][7]

MIF contains two motifs with catalytic activity. The first is a 27 amino acid motif located at the N-terminus functions as a phenylpyruvate tautomerase that can catalyze the conversion of 2-carboxy-2,3-dihydroindole-5,6-quinone (dopachrome) into 5,6-dihydroxyindole-2-carboxylic acid (DHICA).^[8][9] MIF also contains a Cys-Ala-Leu-Cys catalytic site between residues 57 and 60 that appears to function as a disulfide reductase.^[10]

This gene encodes a lymphokine involved in cell-mediated immunity, immunoregulation, and inflammation.^[11][12][13] MIF plays a role in the regulation of macrophage function in host defense through the suppression of anti-inflammatory effects of glucocorticoids.^[13][14][15] This lymphokine and the JAB1 protein form a complex in the cytosol near the peripheral plasma membrane, which may indicate a role in integrin signaling pathways.^[16]

MIF binds to CD74,^[17] inducing its phosphorylation and the recruitment of CD44 which then activates non-receptor tyrosine kinases, leading ultimately to extracellular signal-regulated kinase phosphorylation.^[18]

Macrophage migration inhibitory factor has been reported to interact with:

• BNIPL,^[19]
• CD74,^{[20][21][22][23][24]}
• COPS5,^[25]
• CXCR4,^[26][27][28] and
• RPS19.^[29]

MIF is an inflammatory mediator associated with rheumatoid arthritis (RA) severity.^[30][31][32] MIF protein levels are increased in the plasma of people with schizophrenia, including people in the early stages of the illness, but the clinical significance of this has not been determined.^[33][34] Macrophage migration inhibitory factor is also a potential drug target for sepsis, rheumatoid arthritis, and cancer.^[35] It has also been shown to induce changes in the heart during sepsis.^[36]

Evidence suggests that there is a correlation between MIF production and metastatic potential in colorectal cancer.^[37]

It has been reported that there is increased MIF production in Alzheimer’s disease and mild cognitive impairment.^[38] It has further been reported that this enzyme, in Alzheimer’s disease, undergoes glycation and oxidation, inhibiting its activity.^[39]