Figure 8 is a schematic representation of α2M* counteracting the antagonist effect of aggLDL on LRP1, improving the insulin response characterized by PI3K/Akt and MAPK/ERK signaling activation as well as GLUT4 translocation to PM and glucose uptake in cardiomyocytes. All our findings may have important therapeutic implications in relation to the role of α2M* in the cardiac insulin response associated with hypercholesterolemia. Here, LRP1 is linked to familial hypercholesterolemia.