Disturbance of the palmitoylation of IRHOM2 by ZDHHC3 deletion in hepatocytes or 2‐bromopalmitate (2‐BP), a general inhibitor of protein S‐palmitoylation, mitigates the symptoms in rodent and rabbit models with the NASH phenotype, thus also indicating a potential promising therapeutic strategy for the treatment of NASH. This evidence concerns the gene RHBDF2 and metabolic dysfunction-associated steatohepatitis.