A study reports a new genetic factor that influences LDL-cholesterol (LDL-C) levels, revealing a potential novel mechanism of lipid homeostasis. An array-based association analysis in 1,102 Amish individuals identified a variant in chromosome 5 that was associated with a 15 mg/dl increase in LDL-C levels. Genetic analyses indicated eight candidate genes in this region and functional studies in zebrafish showed that overexpression of one of the candidates, the transcribed pseudogene APOOP1, increased LDL-C levels and vascular plaque formation. Further assays provided a possible regulatory link to its parent gene, APOO (encoding apolipoprotein O), suggesting APOO as a novel target for hyperlipidaemia.