TNF‐α is a proinflammatory cytokine that contributes to the second hit in NASH pathogenesis.23 Thus, our results provide new insight to elucidate the function of PNPLA3 I148M mutant protein and its role in NAFLD and explain why NAFLD patients carrying the PNPLA3 148M are more susceptible to progressive NAFLD. This evidence concerns the gene PNPLA3 and metabolic dysfunction-associated steatohepatitis.