Macrophage migration inhibitory factor (MIF) is a cytokine that plays a crucial role in innate immunity. Discovered over 40 years ago, MIF was initially poorly understood but has since been shown to regulate immune responses and inflammatory processes. MIF is constitutively expressed by various immune and non-immune cells, including macrophages, monocytes, and cells in the endocrine system. It is involved in the detection and response to pathogens, and its expression is linked to the severity of diseases such as sepsis and autoimmune disorders. MIF acts through multiple mechanisms, including the activation of signaling pathways like ERK1/ERK2, upregulation of TLR4, and modulation of inflammatory responses. It also counteracts the immunosuppressive effects of glucocorticoids and inhibits p53-mediated apoptosis. MIF is implicated in the pathogenesis of sepsis, inflammatory diseases, and autoimmune conditions. Therapeutic strategies targeting MIF, such as MIF-specific antibodies, have shown promise in reducing inflammation and improving survival in sepsis and other inflammatory diseases. MIF's role in innate immunity highlights its importance in host defense against infections and its potential as a therapeutic target for immune-related disorders.Macrophage migration inhibitory factor (MIF) is a cytokine that plays a crucial role in innate immunity. Discovered over 40 years ago, MIF was initially poorly understood but has since been shown to regulate immune responses and inflammatory processes. MIF is constitutively expressed by various immune and non-immune cells, including macrophages, monocytes, and cells in the endocrine system. It is involved in the detection and response to pathogens, and its expression is linked to the severity of diseases such as sepsis and autoimmune disorders. MIF acts through multiple mechanisms, including the activation of signaling pathways like ERK1/ERK2, upregulation of TLR4, and modulation of inflammatory responses. It also counteracts the immunosuppressive effects of glucocorticoids and inhibits p53-mediated apoptosis. MIF is implicated in the pathogenesis of sepsis, inflammatory diseases, and autoimmune conditions. Therapeutic strategies targeting MIF, such as MIF-specific antibodies, have shown promise in reducing inflammation and improving survival in sepsis and other inflammatory diseases. MIF's role in innate immunity highlights its importance in host defense against infections and its potential as a therapeutic target for immune-related disorders.