SMPD1 and Niemann-Pick disease type A: Previous studies reported that TNFα could activate NF-κB by ceramide produced by ASM hydrolyzing sphingomyelin in immune cells [40] whereas Kuno 1994 and Zumbansen 1997 et al. [49, 50] suggested TNFα could activate NF-κB in ASM-deficient Niemann-Pick disease type A fibroblasts and ASM knockout embryonic fibroblasts, suggesting the activation of NF-κB is through the canonical signaling pathway without relying on the ASM.