Our previous study demonstrated that global inhibition of megalin by antisense oligonucleotides (ASO) administration attenuated hypercholesterolemia-induced atherosclerosis in both male and female mice, accompanied by diminished protein abundance of AGT and renin in renal PTCs as well as renal AngII concentrations.7 These findings support the hypothesis that megalin contributes to atherosclerosis by interacting with the renin-angiotensin components in PTCs. The gene discussed is LRP2; the disease is familial hypercholesterolemia.