Gaussia luciferase (Gluc) is a sensitive reporter for studying different biological processes such as gene expression, promoter activity, protein-protein interactions, signal transduction, as well as tumor cell growth and response to therapy. Since Gluc is naturally secreted, the kinetics of these processes can be monitored in real-time by measuring an aliquot of conditioned medium in culture or a few microliters of blood in vivo at different time points. Gluc catalyzes light emission with a short half-life which is unfavorable for certain applications. We isolated a Gluc mutant that catalyzes enhanced light stability in the presence of a detergent, in combination with high sensitivity, making it an attractive luciferase for high-throughput functional screening applications.