• Membrane proteins (MPs) play essential roles in biological and pharmacological processes. Many of them require cholesterol (CHOL) as their structure supportive lipid component and modulator for functionality. Unfortunately, commercially available CHOL and its derivatives have limitations on solubility or bio-activity. • We report 4-((cholesteryloxy)-4-oxobut-2-enamido)ethyl) dimethylam-monio) propane-1-sulfonate (CHEAPS), a novel CHOL alternative for MP study. CHEAPS can be readily solubilized in both detergents and membrane-active polymers. Interestingly, it could stabilize and support a new discovered enzyme function of human mitochondrial TSPO. As such CHEAPS may have a broad application for MP structural biology.
