NPC1L1

Official Full Name

NPC1 like intracellular cholesterol transporter 1

Organism

Homo sapiens

Gene ID

29881

Background

The protein encoded by this gene is a multi-pass membrane protein. It contains a conserved N-terminal Niemann-Pick C1 (NPC1) domain and a putative sterol-sensing domain (SSD) which includes a YQRL motif functioning as a plasma membrane to trans-Golgi network transport signal in other proteins. This protein takes up free cholesterol into cells through vesicular endocytosis and plays a critical role in the absorption of intestinal cholesterol. It also has the ability to transport alpha-tocopherol (vitamin E). The drug ezetimibe targets this protein and inhibits the absorption of intestinal cholesterol and alpha-tocopherol. In addition, this protein may play a critical role in regulating lipid metabolism. Polymorphic variations in this gene are associated with plasma total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels and coronary heart disease (CHD) risk. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]

Synonyms

LDLCQ7; NPC11L1; SLC65A2

Cat.No.	Product Name	Price
CSC-DC010541	Panoply™ Human NPC1L1 Knockdown Stable Cell Line	Inquiry
CSC-SC010541	Panoply™ Human NPC1L1 Over-expressing Stable Cell Line	Inquiry

Cat.No.	Product Name	Price
AD10931Z	Human NPC1L1 adenoviral particles	Inquiry
LV19771L	human NPC1L1 (NM_013389) lentivirus particles	Inquiry
LV19772L	human NPC1L1 (NM_001101648) lentivirus particles	Inquiry

Cat.No.	Product Name	Price
SHH354104	shRNA set against Human NPC1L1 (NM_013389.2)	Inquiry
SHH354108	shRNA set against Mouse NPC1L1 (NM_207242.2)	Inquiry
SHR017598	shRNA set against Human NPC1L1(NM_013389.2)	Inquiry
SHR017634	shRNA set against Rat Npc1l1(NM_001002025.1)	Inquiry

Cat.No.	Product Name	Price
OE-PNDC000160	Human NPC1L1 Nanodisc	Inquiry
OE-PNDC000789	Human NPC1L1 Nanodisc	Inquiry

Cat.No.	Product Name	Price
CDCR277012	Mouse Npc1l1 ORF Clone(NM_207242.2)	Inquiry
CDCS419151	Human NPC1L1 ORF Clone (BC117178)	Inquiry
CDFH012702	Human NPC1L1 cDNA Clone(NM_001101648.1)	Inquiry
CDFL008490	Mouse Npc1l1 cDNA Clone(NM_207242.2)	Inquiry
CDFR001190	Rat Npc1l1 cDNA Clone(NM_001002025.1)	Inquiry
MiUTR1H-06872	NPC1L1 miRNA 3'UTR clone	Inquiry
MiUTR1R-04249	NPC1L1 miRNA 3'UTR clone	Inquiry
MiUTR3H-09661	NPC1L1 miRNA 3'UTR clone	Inquiry
CDCB181177	Rabbit NPC1L1 ORF clone (NM_001082228.1)	Inquiry
CDCL139363	Human NPC1L1 ORF clone (NM_001101648.1)	Inquiry
CDCL139365	Human NPC1L1 ORF clone (NM_013389.2)	Inquiry
CDCR368237	Rat Npc1l1 ORF Clone(NM_001002025.1)	Inquiry

Detailed Information

Niemann-Pick C1-Like 1 (NPC1L1) is a key transporter for cholesterol absorption in the intestine. NPC1L1 is present on the brush border membrane of small intestinal epithelial cells and affects cholesterol absorption and plasma low-density lipoprotein levels. It is an important factor in maintaining the cholesterol metabolism balance in the body, and it is also the target of the new lipid-lowering drug ezetimibe.

NPC1L1 Figure 1. Ezetimibe treatment reduced brain infarction, improved short-term and long-term neurological function. (Jing, Y., et al. 2018)

Tissue Distribution of NPC1L1

The amino acid sequence of NPC1L1 is 40% identical to NPC1, and like NPC1, there is a signal peptide at the N-terminus and a sterol-sensitive region in the middle. The expression distribution of NPC1L1 is species-specific. In mice, it is mainly expressed in the small intestine. In humans, in addition to the small intestine, it is also abundantly expressed in the liver. Studies have shown that NPC1L1 is present in the brush border membrane of the intestinal epithelial cells and the bile duct membrane of the liver. The intestinal absorption level of cholesterol in NPC1L1 knockout mice was about half that of wild-type mice, and the remaining low levels of cholesterol were not sensitive to ezetimibe treatment. Furthermore, feeding high-cholesterol diets to knockout mice did not induce hypercholesterolemia, nor did they produce fatty liver.

NPC1L1 and Phytosterols

Studies have shown that in transgenic mice expressing a large number of NPC1L1, the absorption of cholesterol in the diet decreased by 50%, and the concentration of cholesterol in bile increased by a factor of five. Compared to cholesterol, phytosterols are difficult to be absorbed, and it is unclear whether phytosterols and cholesterol are absorbed into intestinal epithelial cells through the same mechanism. In NPC1L1 knockout or NPC1L1/ AB-CG5 /ABCG8 knockout mice, plasma levels of phytosterols, campesterol and sitosterol were almost undetectable. In addition, domestic mice have also been reduced by more than 90% compared to wild-type mice. In the intestines of NPC1L1 knockout mice, the marked absorption of sitosterol was reduced, which was similar to the observed decrease in the absorption of sitosterol in wild-type mice treated with ezetimibe. These results indicate that NPC1L1 is a transporter of cholesterol and structurally related phytosterol absorption, and that ezetimibe acts to inhibit the NPC1L1 pathway.

NPC1L1 and Disease

Cholesterol is an important component of cell membranes and a precursor of bile acids and steroid hormone synthesis. However, high levels of cholesterol in the blood can cause atherosclerosis, coronary heart disease and heart disease. By inhibiting the expression of NPC1L1 to reduce the cholesterol content in the blood, it has a positive therapeutic effect on the above diseases. Studies have shown that in ApoE knockout mice, ezetimibe can reduce the absorption of cholesterol, reduce the cholesterol content in the blood, and effectively inhibit the further deterioration of atherosclerosis. In mice in which both NPC1L1 and ApoE genes were knocked out, cholesterol absorption was greatly reduced, and the occurrence and development of atherosclerosis were almost completely suppressed.

NPC1L1 also plays an important role in metabolic diseases. Both ezetimibe and knockout NPC1L1 have effective therapeutic effects on metabolic diseases. Ezetimibe inhibits the steatosis of the liver by reducing the absorption of cholesterol, thus playing an effective role in treating non-alcoholic fatty liver. NPC1L1 knockout mice can prevent fatty liver formation even when fed with high fat. In addition, inhibition of NPC1L1 can also effectively improve insulin tolerance. These studies indicate that NPC1L1 plays a key role in the pathogenesis of metabolic diseases. Inhibition of NPC1L1 and NPC1L1-mediated intestinal cholesterol absorption will play an effective role in preventing and treating metabolic diseases such as non-alcoholic fatty liver, insulin resistance, and type 2 diabetes.

References:

Jing, Y. , Xue, L. , Nathanael, M. , Devin, M. B. , Jiping, T. , & Min, Y. , et al. (2018). Ezetimibe, a npc1l1 inhibitor, attenuates neuronal apoptosis through ampk dependent autophagy activation after mcao in rats. Experimental Neurology, 307, 12-23.
Cho, Jae-Young, Jang, Beom-Su, Park, & Sang-Hyun, et al. (2015). Evaluation of cholesterol absorption inhibition of anti-npc1l1 igy by [h-3]-labeled cholesterol in sprague-dawley rats. Journal of Radioanalytical and Nuclear Chemistry: An International Journal Dealing with All Aspects and Applications of Nuclear Chemistry.
Yang, H. , Zhou, L. , Okoro, E. , & Guo, Z. M. . (2014). Induction of npc1l1 membrane translocation and cholesterol absorption by cholecystokinin. AtherosclerosisIN , 235(2), e33.

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