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NPC1L1

Products

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

Niemann-Pick C1-like 1 (NPC1L1) is a multipass membrane protein encoded by the NPC1L1 gene on human chromosome 7p13 and comprises approximately 1,332 amino acids. NPC1L1 is an evolutionary paralog of the lysosomal cholesterol transporter NPC1 and shares a conserved architecture that includes a sterol-sensing domain (SSD) and an N-terminal domain (NTD) involved in sterol recognition. Its protein topology consists of 13 transmembrane helices, with several large extracellular or luminal loops and cytoplasmic loop regions. The NTD contains a hydrophobic sterol-binding cavity, while extracellular regions of NPC1L1 are also relevant to inhibitor-binding research. NPC1L1 is primarily localized to the apical membrane of absorptive epithelial cells and plays a central role in intestinal sterol uptake and cholesterol homeostasis. Ligand-dependent and membrane-trafficking mechanisms regulate NPC1L1 internalization and recycling, including clathrin/AP2-associated endocytic processes. Genetic and functional studies have established NPC1L1 as an important regulator of cholesterol absorption, making its sterol-binding, membrane trafficking, and inhibitor-interaction mechanisms important areas of metabolic research.

Fig.1 Hepatic cholesterol metabolism via NPC1L1. (OA Literature)Fig.1 Hepatic cholesterol metabolism, transport, and biliary regulation.1

NPC1L1 Transporter Function: Orchestrating Enterohepatic Cholesterol Flux

The functional breadth of NPC1L1 spans multiple physiological and therapeutic contexts:

  • Intestinal Cholesterol Absorption: NPC1L1 forms clathrin-coated pit at the brush border membrane and binds free cholesterol thus initiating the primary entry route for dietary cholesterol via intestinal absorption of an egg yolk sized batch each time. This is the major pathway for intestinal sterol absorption, and one that ezetimibe works to inhibit.
  • Hepatic Biliary Cholesterol Reabsorption: In humans, canalicular NPC1L1 extracts cholesterol from bile and opposes ABCG5/G8-mediated secretion. This enterohepatic recirculation not only preserves endogenously stores of cholesterol but may also protect hepatocytes from hydrophobic bile acid cytotoxicity.
  • Plant Sterol Discrimination: NPC1L1 promotes intestinal absorption of both cholesterol and plant sterols like sitosterol/campesterol but has a greater affinity for cholesterol. This subtype specificity defines NPC1L1 as the first genetically identified defense mechanism against phytosterol accumulation, working in concert with the ABCG5/G8 efflux machinery.

NPC1L1 Membrane Protein Product

Creative Biolabs provides NPC1L1 protein constructs and preparations suitable for structural biology, sterol-binding studies, inhibitor-interaction research, and antibody research. Our engineering team designs NPC1L1 constructs according to specific experimental requirements, with consideration of structural regions involved in sterol recognition and membrane-associated function, including the N-terminal domain (NTD) and sterol-sensing domain (SSD). Available construct formats and preparation strategies can be selected according to the intended research application, such as structural characterization, binding studies, or compound screening.

NPC1L1 Protein Product

Not finding the membrane protein product you need? Contact us to start your one-stop custom service!

NPC1L1 Stable Cell Line Product

Uptake assays, inhibitor screening and enterohepatic transport studies require reliable cellular models that express functional NPC1L1 at the apical membrane which support cholesterol-dependent endocytic activity. We engineered custom NPC1L1 stable cell lines, by using optimized transduction and selection protocols to establish homogeneous long-term transporter expression within a sustained framework of appropriate lipid composition. Our platform provides highly precise genetic control through lentiviral delivery, transposon coupling integration and a targeted knock-in system. Every line is subjected to stringent monoclonal selection for clonal purity and extensive phenotypic confirmation defining not only surface transporter density, but also total sterol uptake in response to ezetimibe.

NPC1L1 Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

NPC1L1 Recombinant Antibody Product

High-affinity, sequence-defined antibodies to NPC1L1 are required for identifying the transporter in gut and liver tissue, determining its brush border and canalicular localization and inhibiting cholesterol uptake when used therapeutically. Creative Biolabs provides complete recombinant antibody discovery programs targeting both the extracellular and intracellular NPC1L1 epitopes. Our antibody development pipeline, from immunogen design and multi-platform selection through downstream engineering for binders providing the specificity, affinity, and developability characteristics needed for research onwards. Utilizing recombinant expression and clonal sequencing removes batch-to-batch variability that is often problematic with traditional polyclonal sera, giving a fully characterized, renewable reagent.

NPC1L1 Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • High Purity & Activity: High purity and verified integrity for dependable downstream work.
  • Diverse Expression Systems: Choice of expression formats to match routine or specialized projects.
  • Species Reactivity: Products available for human, mouse, pig, and other species.
  • Validated Applications: Application-tested to deliver consistent signals across common lab workflows.
  • Superior Batch-to-Batch Consistency: Stringent quality controls to ensure low variability from batch to batch.
  • Customization Options: Tags/Labels/package Modifications available upon request.

Custom NPC1L1 Membrane Protein and Antibody Discovery Services

Complementing its standard catalog products, Creative Biolabs provides sophisticated discovery services to meet the complete range of NPC1L1 research needs:

  • Production & Validation: Cloning of the synthesized optimized gene into an expression vector, plus small-scale expression trials to help determine the best expression conditions.
  • Custom Antibody Production: Produced via large-scale expression in mammalian/insect/cell culture or bacterial expression systems, purified in detergent or reconstituted into nanodiscs.
  • Engineered Cell Lines: Creation of stable cell lines that physiologically mimic endogenous NPC1L1 expression and activity.
  • Functional Assessment Systems: Designing and executing assays to assess protein function and ligand binding.

Frequently Asked Questions (FAQ)

  1. Is there a stable cell line available which enables continuous cholesterol uptake/brush-border trafficking and ezetimibe-blockade kinetics modelling in response to the constitutive expression of full-length NPC1L1 from an integrated transgene cassette while retaining an intact polarized intestinal epithelial background?

    Yes. We constructed stable lines that show strong apical NPC1L1 expression as determined by domain-specific biotinylation and confocal microscopy. The standardization of each batch, as indicated by the accompanying data on radiolabeled cholesterol uptake velocity and ezetimibe-inhibitable transport allows for seamless mechanistic research without repeated transient transfection in a single cell type.

  2. Can your anti-NPC1L1 antibodies be used for immunofluorescence to detect enterocyte and canalicular distribution in formalin-fixed, paraffin-embedded intestinal villus or hepatobiliary tissue sections?

    Yes. Using selected clones on archival gastrointestinal tissue following antigen retrieval, we have achieved specific apical brush-border and intracellular vesicular staining patterns consistent with an enterocyte and biliary epithelium distribution.

  3. Do you provide NPC1L1 variants with characterized loss-of-function or trafficking-defective mutations for implementation of comparative cholesterol affinity and membrane targeting analyses?

    Yes. We provide recombinant proteins as well as stable cell lines that express characterized variants with altered sterol-sensing domain residues or endocytic motifs disrupted.

  4. Is your recombinant NPC1L1 supplied in a mild detergent formulation that permits direct insertion into cholesterol-loaded proteoliposomes or planar lipid bilayers for reconstituted sterol transport and inhibitor-binding studies?

    Yes. The purified protein is then concentrated in a physiologic pH non-ionic detergent buffer and finally buffer-exchanged into a lipid-compatible system. This allows immediate reconstitution into synthetic membranes for stopped-flow, fluorescence or radiolabeled cholesterol flux assays without additional dialysis.

Reference
  1. Chen, Pei-Yi, et al. "Niemann–Pick C1-Like 1 in Cholesterol Absorption and Homeostasis: Mechanisms, Regulation, and Emerging Phytochemical Inhibitors." Current Issues in Molecular Biology 48.6 (2026): 592. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.3390/cimb48060592
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