Although the oncogenic property of PTP4A1 overexpression and the restricted beneficial effects of PTP4A1-mediated FGF21 remain a hurdle to developing a therapeutic target, PTP4A1-mediated CREBH activation might be considered one of the strategies to elevate FGF21 levels in metabolic disorders, including NAFLD. The gene discussed is PTP4A1; the disease is metabolic dysfunction-associated steatotic liver disease.