To sum up, penfluridol is a newly found drug that can inhibit TNFα-induced NF-κB activity by targeting ASM that penfluridol binds to, thus reduces ASM activity, which not only provides further understanding of the treatment mechanism for penfluridol but also broadens new possible applications of penfluridol to autoimmune diseases and elevated ASM activity-related diseases, in addition to the well-known role in treating chronic schizophrenia. Here, SMPD1 is linked to autoimmune disease.