RHBDF2 and metabolic syndrome: In summary, as shown in Figure 8, our current study provides a new insight into steatohepatitis pathogenesis and targeting IRHOM2 palmitoylated regulation by over‐nutrition intake‐associated signals, and proposes a novel molecular vicious circle mediated by ZDHHC3‐IRHOM2 axis and involving posttranslational regulation of IRHOM2, potentially further linking metabolic syndrome and its complications.