To investigate whether palmitoylated IRHOM2 was involved in fatty liver diseases, we first examined its expression profile alterations upon 2‐bromopalmitate (2‐BP), a general inhibitor of protein palmitoylation challenge.[25] When human hepatocyte THLE2 cells were incubated with a concentration gradient of 2‐BP to downregulate palmitoylated proteins (Supplementary Figure S1a), the IRHOM2 protein expression was markedly reduced in both dose‐dependent (Figure 1a) and time‐dependent manners (Figure 1b). Here, RHBDF2 is linked to fatty liver disease.