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We performed a siRNA kinase and phosphatase screen in HuH\u20107 cells using high\u2010content automated imaging of LDs. Changes in accumulated lipids were quantified with developed pipeline that measures intensity, area, and number of LDs. Selected \u201chits,\u201d which reduced lipid accumulation, were further validated with other lipid and expression assays. Among several siRNAs that resulted in significantly reduced LDs, one was targeted to the nuclear adapter protein, transformation\/transcription domain\u2010associated protein (TRRAP). Knockdown of TRRAP reduced triglyceride accumulation in HuH\u20107 hepatocytes, in part by reducing C\/EBP\u03b1\u2010mediated de novo synthesis of TGs. These findings implicate TRRAP as a novel regulator of hepatic TG metabolism and nominate it as a potential drug target for hepatosteatosis.<\/jats:p>","DOI":"10.1111\/cts.12988","type":"journal-article","created":{"date-parts":[[2021,6,22]],"date-time":"2021-06-22T10:49:45Z","timestamp":1624358985000},"page":"1369-1379","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Lipid droplet screen in human hepatocytes identifies TRRAP as a regulator of cellular triglyceride metabolism"],"prefix":"10.1111","volume":"14","author":[{"given":"Deepti","family":"Abbey","sequence":"first","affiliation":[{"name":"Department of Genetics University of Pennsylvania Philadelphia Pennsylvania USA"},{"name":"Division of Translational Medicine and Human Genetics Department of Medicine University of Pennsylvania Philadelphia Pennsylvania 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