Methods and compositions for assaying an agent for TERT promoter modulatory activity are provided. In the subject methods, an agent is contacted with a cell comprising a mutant telomerase structural RNA component (TR) that results in a detectable phenotype in the presence of telomerase reverse transcriptase (TERT). Also provided are compositions, systems and kits thereof, as well as devices, that find use in practicing the subject methods. The subject invention finds use in assaying agents for TERT promoter modulatory activity, such as in a high throughput format.