Protein neddylation, a newly characterized posttranslational modification that 
adds the ubiquitin-like molecule NEDD8 to substrates, modulates important 
biological processes, whereas dysfunction of neddylation may cause several 
serious diseases, such as cancer. Inhibition of neddylation pathway has emerged 
as a promising anticancer strategy, as evidenced by development of the 
NEDD8-activating enzyme (NAE) inhibitor MLN4924. Due to its potent anti-cancer 
efficacy and well-tolerated toxicity, MLN4924 has been evaluated in multiple 
Phase I clinical trials for solid tumors and hematologic malignancies. Recently, 
accumulating evidences indicate that neddylation pathway also plays a pivotal 
role in the regulation of multiple processes of tumor microenvironment (TME), 
such as tumor angiogenesis and the function of immune cells. In this review, we 
briefly summarize the latest progresses in this field and highlight neddylation 
pathway as an attractive therapeutic target against human cancer.