LAUSR

Human genetic studies have established the orphan G proteincoupled receptor gene, GPR146, as a regulator of plasma cholesterol levels. In line with these findings, Yu et al. report that depletion of GPR146 in mice substantially reduces circulating LDLcholesterol and triglyceride levels, through activation of ERK signalling and promotion of SREBP2 activity. The lipidlowering effects of GPR146 depletion protected mice against atherosclerosis in an LDL receptor (LDLR)-independent manner, reducing lesion area by up to 90%. Injection of LDLR−/− mice with an AAVdelivered shRNA targeting GPR146 lowered plasma total cholesterol levels.