The clathrin adaptor Numb regulates intestinal cholesterol absorption through dynamic interaction with NPC1L1

Bao-Liang Song and colleagues report that the clathrin adaptor Numb recognizes a peptide motif within the cholesterol transporter NPC1L1 upon cholesterol binding and thus facilitates dietary cholesterol uptake into the gut. Inhibition of this Numb-NPC1L1 interaction in mice reduces serum cholesterol levels and thus may be a therapeutic target to treat hypercholesterolemia in the clinic.