Whether sequence substitutions of H327 and Y336 in the EGF-A domain of LDLR (Figure S3) into the Q2954 and F2963 substitutions in LRP-1 result in a lower affinity for PCSK9, as predicted from our results (Figures 2 and 3), is not known, but may in part explain the lower efficacy of PCSK9 to enhance the degradation of LRP-1 compared to LDLR in most cell types, except for melanoma B16 cells. Here, LDLR is linked to melanoma.