LDLR and familial hypercholesterolemia: In the present study, we analyzed the function of the LRP6 LDLRR by mutational approaches and showed that substitutions of LRP6 LDLRR amino acids, which are highly conserved with residues in the LDLR causing familial hypercholesterolemia (FH), inhibited LRP6 internalization and Wnt signaling activity.