During RCC progression, this neural network undergoes malignant remodeling: Clinicopathological studies have confirmed that the synaptic protein NPTX2 (which is not expressed in healthy kidneys) is aberrantly overexpressed in ccRCC, where it activates the PI3K-Akt pro-survival pathway via binding to the AMPA receptor GluA4 (8). Here, NPTX2 is linked to renal cell carcinoma.