To investigate this role of LRP1 tyrosine phosphorylation in atherosclerosis, we developed a knock-in mouse model in which the tyrosine in the distal NPxY motif was replaced with phenylalanine (Lrp1Y63F), thereby disabling Lrp1 NPxY phosphorylation while leaving the interaction with phosphotyrosine-independent PTB-domain containing adaptor proteins intact (Gotthardt et al., 2000; Trommsdorff et al., 1998). The gene discussed is LRP1; the disease is atherosclerosis.