Mechanistically, the high reserve-accelerated decline phenotype in Class 2 patients aligns closely with previously reported metabolic crisis characteristics (3) —lactic acid accumulation in the tumor microenvironment activates adipose tissue GPR81 receptors, triggering fat browning and muscle breakdown via the Gi-Gβγ-RhoA/ROCK1-p38 signaling axis. The gene discussed is CFB; the disease is neoplasm.