SMAD2 and renal cell carcinoma: Monitoring TGF-β pathway activity (e.g., p-Smad2/3) and manganese metabolism-related proteins (e.g., ZIP8, MnSOD) could potentially predict RCC progression. Similarly, the PI3K/AKT/mTOR signalling pathway—a star molecular pathway—promotes cell proliferation, survival, angiogenesis, and metabolic adaptation (including enhanced glycolysis), making it a key therapeutic target in RCC [52].