Critical challenges include confounders (high-fiber diets increase fecal acetate by 2.1-fold; vancomycin cuts serum acetate by 60% in mice) and delivery—targeted strategies (ex vivo T cell ACSS2 upregulation, pH-sensitive nanoparticles for tumor-specific release) are essential to avoid off-target effects (e.g., tumor lipid biosynthesis; 112, 115). The gene discussed is ACSS2; the disease is neoplasm.