Furthermore, given that we have determined the IRHOM2 S‐palmitoylation occurred and exhibited a positive correlation with dysregulated lipid metabolism during NASH, to additionally confirm PAOA‐induced increase of IRHOM2 S‐palmitoylation contributed to abnormal lipid metabolism, adenovirus‐mediated IRHOM2 knockdown (AdshIRHOM2) transfected‐, 2‐BP treated‐ or 2‐BP+AdshIRHOM2 cotreated‐THLE2 cells were used respectively to suppress palmitoylation, IRHOM2 expression levels, and palmitoylated IRHOM2 expression, followed by detection of intracellular lipid deposition. This evidence concerns the gene RHBDF2 and metabolic dysfunction-associated steatohepatitis.