Enhanced F‐actin assembly and elongation leading to increased filopodia formation and motility of GBM are clinically relevant phenotypes of the Cdc42‐mediated cytoskeletal signature activated by the novel CTRP8/RLN2‐RXFP1‐JAK3‐STAT3 cascade in human glioma. Here, STAT3 is linked to central nervous system cancer.