Protein expression in mammalian cells is key for the production and manufacturing of bio-therapeutics with human-like properties and activities. As a molecular basis for reaching high protein expression levels, efficient promoter/enhancer systems are a prerequisite. Here we identify a novel enhancer from the mouse cytomegalovirus (CMV) immediate early 2 (IE2) region as a strong expression-promoting element. We further demonstrate its activity in bi-directional promoter architecture and apply it to generate production clones for IL-18BP, a protein with therapeutic indications in autoimmune diseases. These data show that the IE region from mouse CMV, and the IE2 enhancer/promoter in particular, have a broad potential for application in novel gene expression systems for research, development, and manufacturing of protein drugs.