SPP1 deficiency may reduce liver-related mortality, which may be associated with the promotion of a systemic pro-inflammatory milieu by SPP1. This suggests that SPP1 plays a dual role in the pathogenesis of fatty liver and that SPP1 may be involved in the internal control of excessive lipid uptake in the liver, thereby protecting the liver from lipotoxicity, apoptosis, and subsequent fibrosis and hepatocyte proliferation (26). The gene discussed is SPP1; the disease is fatty liver disease.