Specifically, NPC1L1 downregulation may reflect a metabolic adaptation in RCC development, where the Warburg effect shifts energy production towards glycolysis, and the effective capabilities of SR-B1 and VLDL-R to transfer cholesterol in bulk from HDL and VLDL—unlike the absorption of individual cholesterol molecules by NPC1L1—adequately meets the tumor’s initial cholesterol demands. The gene discussed is NPC1L1; the disease is neoplasm.