Niemann-Pick C1-like protein 1 (NPC1L1)

Function

• role in cholesterol homeostasis
• role in uptake of cholesterol across plasma membrane of intestinal enterocyte
• role in transport of multiple lipids
• role in regulating lipid metabolism & homeostasis

Structure

• belongs to the patched family
• contains 1 SSD (sterol-sensing) domain
• highly glycosylated

Compartment

• apical cell membrane
• cytoplasmic vesicle membrane fraction, rich in RAB5

Alternative splicing

named isoforms=3

Expression

• widely expressed
• expressed in liver, small intestine, pancreas, kidney, lung, pancreas, spleen, heart, gall bladder, brain, testis, stomach, muscle
• downregulated in Caco-2 cells upon PPARD activation

Pathology

• lack of activity leads to multiple lipid transport defects

Polymorphism

• variations in NPC1L1 gene could be associated with response to ezetimibe treatment
• variations in NPC1L1 that inhibit its function that lower plasma LDL cholesterol levels & a reduce the risk of coronary artery disease

Pharmacology

• ezetimibe, a drug that inhibits cholesterol absorbtion, directly inhibits NPC1L1

More general terms

• transmembrane 13 protein
• glycoprotein
• carrier protein (transporter)

Database

• OMIM: https://mirror.omim.org/entry/608010
• UniProt: http://www.uniprot.org/uniprot/Q9UHC9.html