By establishing a mouse model of LPS-induced AKI, Xiong et al. demonstrated that acid sphingomyelinase (ASM) promotes EVs secretion by macrophages, and these Exos are internalized by surrounding endothelial cells, inducing damage to GECs, whereas amitriptyline, an ASM inhibitor, reduces the release of EXOs after LPS stimulation and inhibited endothelial cell damage by EVs, which provides a new target for S-AKI treatment [78]. The gene discussed is SMPD1; the disease is acute kidney injury.