Legumain (LGMN; EC: 188.8.131.52), an asparaginyl endopeptidase (AEP) or asparaginyl carboxypeptidase
(ACP), is a member of the C13 family of cysteine proteases. Elevated expression of LGMN is reported not only in the
tumor cells of breast, prostate and liver but also in the macrophages of the tumor micro-environment. Hence, LGMN is
considered as a key protein involved in the regulation of tumor angiogenesis, invasion and metastasis. Targeting LGMN
using siRNA or pharmacological agents and peptides was reported to reduce cancer cells proliferation in vitro and shrink
tumor size in vivo. Moreover, expression of LGMN is significantly lower in normal cells compared to tumor cells or
tumor associated macrophages (TAMs), hence, legumain can be used as a marker for tumor recognition and targeting.
Therefore, approaches inhibiting LGMN expression or activity are more viable, less toxic and help in developing the
targeted therapeutics. However, to date, LGMN targeting strategies have not been well reported. In this review, an attempt
was made to summarize articles pertaining to LGMN (a) structure and activity; (b) oncogenic nature; (c) pharmacological
inhibitors; and (d) targeting approaches that inhibit tumor growth. Furthermore, a list of existing gaps in LGMN research
is highlighted, which needs additional studies.