a2 -Macroglobulin (a2M) is an abundant glycoprotein with the intrinsic capacity for capturing diverse proteins for rapid delivery into cells. After internalization by the receptor-mediated endocytosis,a2M-protein complexes were rapidly degraded in the endolysosome system. Although this is an importantpathway for clearanceofbotha2Mandbiological targets, little is known about the nature ofa2M degradation in the endolysosome system.