Researchers found that OTUB1 directly binds to TRAF6 and removes K63-linked polyubiquitination modifications on TRAF6 through its deubiquitinating enzyme activity, an effect that inhibits TRAF6-mediated ubiquitination and activation of ASK1, which in turn down-regulates the expression of lipid metabolism-related genes (CD36, Fabp1, Scd1, PPARG and PPARα) and collagen-related genes (Col1a1, Col3a1, and α-SMA), which ultimately attenuated NASH (46). This evidence concerns the gene MAP3K5 and metabolic dysfunction-associated steatohepatitis.