Biochemistry · Protein
LDL receptor !
The LDL receptor pulls LDL particles out of the blood into the cell; when it fails, LDL cholesterol is high from birth.
Updated 2026-11-01
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Key facts
- It recognises ApoB-100 on LDL and ApoE on IDL and remnants.
- Receptor-mediated endocytosis in clathrin-coated pits; in the acidic endosome it releases LDL and returns to the membrane.
- The liver carries most receptors and clears most plasma LDL.
- SREBP-2 switches its gene on when the cell lacks cholesterol; PCSK9 sends it for degradation.
- LDLR variants are the most common cause of familial hypercholesterolaemia.
- Also called
- LDLR
- Genes
- LDLR
- Structure (PDB)
- 1N7D
Structure
- An 860-residue protein: ligand-binding domain (cysteine-rich repeats that bind calcium), EGF-precursor-like domain, glycosylated region, transmembrane segment and a cytoplasmic tail with the NPxY signal.
- Structure 1N7D shows the extracellular domain at acidic pH, folded back on itself: this is how it lets go of LDL in the endosome.
Regulation
- SREBP-2 raises its transcription when cell cholesterol falls.
- PCSK9 binds its EGF-A domain and stops it recycling: it is degraded in the lysosome.
- IDOL, an LXR-induced ubiquitin ligase, also degrades it.
Inhibitors and toxins
- Not a direct target: statins, ezetimibe and PCSK9 inhibitors increase its numbers.
Clinical notes
- With one faulty copy LDL is often doubled; with two it can be four or more times normal and cause heart attacks in childhood.
- Statins and PCSK9 inhibitors work through the receptor: with no functional receptors the response is poor.
- Hypothyroidism reduces LDL receptors and raises cholesterol.
Related conditions
- Familial hypercholesterolemia
- Atherosclerosis and dyslipidaemia
- Myocardial Infarction (Heart Attack)
- Hypothyroidism
Related
- LDL (low-density lipoprotein)
- PCSK9
- Apolipoprotein B (ApoB-100 and ApoB-48)
- Apolipoprotein E (ApoE)
- Lipoprotein metabolism
- HMG-CoA reductase
Test yourself
Think of the answer, then tap the question to see it.
Which apolipoproteins does the LDL receptor recognise?
ApoB-100 (LDL) and ApoE (IDL and remnants); ApoB-48 does not bind it.
Why does a statin increase liver LDL receptors?
Lower ER cholesterol activates SREBP-2, which induces the LDLR gene.
What happens to the receptor when PCSK9 binds it?
It is internalised with LDL but does not recycle: it is degraded in the lysosome.
Educational information, not medical advice. For any symptom, see a health professional.
Sources: LDLR: Low-density lipoprotein receptor (human) (UniProt, 2026); LDLR gene: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); LDL clearance (R-HSA-8964038) (Reactome, 2026); 1N7D: Extracellular domain of the LDL receptor (RCSB Protein Data Bank, 2026); UniProt P01130: variants (UniProt, 2026).
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Representative model, for educational purposes only.