In the context of metabolic injury, IRHOM2 expression is elevated in hepatocytes and interacts with USP13, which, through its deubiquitination activity, affects the polyubiquitination state of IRHOM2, leading to hyperactivation of downstream signaling pathways (TAK1-JNK and NF-κB p65), exacerbating insulin resistance and mediating pro-inflammatory factors (TNF-α, IL-1b, IL-6, CCL 2, IL-18) are elevated and anti-inflammatory factors (IL-10) are decreased, thereby promoting inflammatory responses (37). Here, MAPK8 is linked to Insulin resistance.