We found that SAMHD1-mediated endocytic FAK signaling promotes lamellipodia formation in ccRCC cells (Fig. 8l), SAMHD1 binds to cortactin to promote early endosome formation and stimulates Rac1 activation via FAK autophosphorylation, and activated Rac1 promotes lamellipodia protrusion, which initiates ccRCC cell migration. The gene discussed is CTTN; the disease is nonpapillary renal cell carcinoma.