A genome‐wide study in metabolic dysfunction‐associated steatotic liver disease (MASLD) uncovers the pivotal role of the active enhancer marker H3K27ac in modulating the key therapeutic target of TDO2, which triggers lipid accumulation and M1 macrophage polarization through NF‐κB activation. The gene discussed is NFKB1; the disease is metabolic dysfunction-associated steatotic liver disease.