Cholesterol/lipid abnormalities, such as high low-density lipoprotein (LDL)/high-density lipoprotein-cholesterol (HDL-C) ratio and elevated circulating triglycerides, are associated with cardiometabolic disorders, including metabolic syndrome, type 2 diabetes mellitus, and atherosclerosis. Cholesterol/lipid homeostasis is controlled by complex gene regulatory circuits involving both transcriptional and posttranscriptional mechanisms. For example, the sterol regulatory element-binding protein (SREBP) 1 and 2 family of transcription factors controls the expression of genes involved in both cholesterol biosynthesis and uptake, as well as fatty acid, phospholipid, and triglyceride production.1 Several groups recently discovered that the human SREBP–encoding genes harbor intronic microRNAs termed miR-33a (present in the SREBF2 gene) and miR-33b (located in the SREBF1 gene).2–6 By contrast with humans and other mammals, rodents lack miR-33b and only have miR-33a in the Srebf2 gene. The miR-33a/b microRNAs, which differ by 2 nucleotides, act in concert with their host gene products to control cholesterol/lipid homeostasis.7 For example, miR-33a/b inhibit the expression of ATP-binding cassette transporter A1 (ABCA1), a cholesterol efflux pump with a key role in reverse cholesterol transport from peripheral tissues such as atherogenic macrophages back to the liver.2–5,8 ABCA1 also promotes the production of nascent lipid-poor HDL-C from the liver and small intestine, and mutation of the ABCA1 gene, as well as aberrant reverse cholesterol transport and low HDL-C levels, has been linked with increased atherosclerosis.9 Intensive efforts have consequently been focused on finding pharmacological tools for increasing circulating HDL-C and promoting reverse cholesterol transport as a novel therapeutic avenue to treat atherosclerosis and cardiovascular …