LDLR Gene

The LDLR gene (LDLR stands for "Low Density Lipoprotein Receptor") is a protein coding gene located on chromosome 19p13.2. Alternative splicing leads to several transcript variants.

The low-density lipoprotein receptor (LDLR) gene family consists of cell surface proteins involved in receptor-mediated endocytosis of specific ligands. The encoded protein is normally bound to the cell membrane, where it binds low-density lipoprotein/cholesterol and is taken up into the cell. Lysosomes release the cholesterol available for repression of the microsomal enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate-limiting step in cholesterol synthesis. At the same time, there is a reciprocal stimulation of cholesterol ester synthesis.

Mutations in this gene cause an autosomal dominant disorder, familial hypercholesterolemia.

1. Bertolini S et al. (2013) Spectrum of mutations and phenotypic expression in patients with autosomal dominant hypercholesterolemia identified in Italy. Atherosclerosis 227:342-348.
2. Stawowy P et al.(2014) PCSK9 as a new target in the therapy of hypercholesterolemia.Heart 39: 466-469.
3. Zhao H et al. (2020) In Vivo AAV-CRISPR/Cas9-Mediated Gene Editing Ameliorates Atherosclerosis in Familial Hypercholesterolemia. Circulation 141:67-79.