For years, TFEB has been regarded as one of the most promising therapeutic targets for restoring the cell's ability to clear and recycle waste. Yet turning that promise into therapies has proved difficult because TFEB itself is hard to target with drugs. Now, a study published in Nature by scientists at the Telethon Institute of Genetics and Medicine (TIGEM) has identified a molecular pathway that controls TFEB activity, uncovering new druggable targets that could open the door to therapies for rare genetic diseases, cancer and other conditions linked to lysosomal dysfunction.