Metabolically, M2/TAMs preferentially engage fatty acid oxidation (FAO) and oxidative phosphorylation, processes strongly driven by hypoxia and nutrient scarcity in the TME (28–30).Mechanistically, reduced expression of RIPK3 (receptor-interacting serine/threonine-protein kinase 3) in hepatocellular carcinoma enhances FAO through transcriptional programs, including activation of the PPAR axis, thereby promoting M2 polarization (31, 32). The gene discussed is RIPK3; the disease is hepatocellular carcinoma.