Collectively, these findings suggest that early signaling prone to lysosomal membrane permeabilization (LMP) is attenuated during the mid-to-late stages of infection through transcriptional suppression of acid sphingomyelinase and key cathepsins, alongside alterations in lysosomal homeostasis, thereby restricting the execution of lysosome-dependent cell death. The gene discussed is SMPD1; the disease is infection.