In a mouse model of acute liver failure, Kim et al. engineered EVs to express SIRPα, a CD47‐binding ligand, enabling preferential accumulation in CD47‐overexpressing necroptotic hepatocytes.[180] These SIRPα‐EVs facilitated immune clearance of damaged cells via macrophage reprogramming and promoted hepatocyte regeneration, exemplifying the dynamic capacity of engineered EVs to reshape tissue microenvironments in vivo. The gene discussed is SIRPA; the disease is acute liver failure.