Fear is a basic emotion that enhances animal survival by triggering the fight, freeze, or flight (3F) response to perceived danger. However, relative little is known about fear at the molecular level. To crack the mystery of fear, we are conducting a forward genetic screen in search of the “fearless” mutant mice. We believe that this unprecedented screen will enable us to identify the core fear genes and elucidate the molecular circuit of fear. These groundbreaking studies could potentially uncover the molecular principles of human emotions and facilitate development of novel treatments for fear-related mental disorders, such as anxiety disorder, phobia, post-traumatic stress disorder (PTSD), and depression.