Cluster of differentiation 74 (CD74) performs multiple roles in B cells, T cells, and antigen-presenting cells within the immune system; it also participates in major histocompatibility complex class II-restricted antigen presentation and inflammation. Recently, a role for CD74 in carcinogenesis has been described. CD74 promotes cell proliferation and motility and prevents cell death in a macrophage migration inhibitory factor-dependent manner. Its roles as an accessory signal receptor on the cell surface and the ability to interact with other signaling molecules make CD74 an attractive therapeutic target for the treatment of cancer. This review focuses on the original role of CD74 in the immune system and its emerging tumor-related functions. First, the structure of CD74 will be summarized. Second, the current understandings about the expression, cellular localization, molecular mechanisms and signaling pathways of CD74 in immunity and cancer will be reviewed. Third, the examples that suggest CD74 is a promising molecular therapeutic target are reviewed and discussed. Although the safety and efficacy of CD74-targeted strategies are under development, deeply understanding of the regulation of CD74 will hold promise for the use of CD74 as a therapeutic target and may develop the CD74-targeted therapeutic agents such as neutralized antibody and compounds.

• Cluster of differentiation 74
• Invariant chain
• Immune
• Inflammation
• Tumorigenesis
• Cancer metastasis