Ubiquitin was identified as a marker of cell injury in nonalcoholic steatohepatitis (NASH), which is now replaced with the term metabolic dysfunction-associated steatohepatitis (MASH) [1,4], and ubiquitylation also plays a vital role in the progression of MASLD via modulating different targets, such as tumor necrosis factor receptor-associated factor 6 (TRAF6), which can promote poly-ubiquitination and the subsequent activation of apoptosis signal-regulating kinase 1 (ASK1) in hepatocytes, thereby aggravating hepatic inflammation and fibrosis during MASH development [5]. The gene discussed is MAP3K5; the disease is metabolic dysfunction-associated steatotic liver disease.