The accumulation of fat in the liver is an increasingly common disease worldwide, with more than a quarter of the world’s population affected. Various causes can lead to the development of fatty liver, with diet and lifestyle being the most common contributors. There is currently no treatment for fatty liver that can stop or reverse the disease. Therefore, researchers have established new human organoid models of fatty liver. They used these models to shed light on drug responses and established a CRISPR screening platform, called FatTracer, to identify new disease mediators and potential therapeutic targets. After screening 35 candidates, a critical new role for the FADS2 (fatty acid desaturase 2) gene in fatty liver disease was discovered. Disruption of FADS2 made the organoids much fatter. Upon overexpression of FADS2, the hepatic steatosis that the organoids once displayed was severely reduced. These models will therefore help test and develop new drugs to treat hepatic steatosis and better understand the biology of the disease. The results of the study will be published in Nature Biotechnology.