Acting as an adapter that bridges the E3-ligase CUL3 and the substrate DDX3X, KLHL29 executes the tumor suppressive function by enhancing the proteasomal degradation of DDX3X, consequently leading to the downregulation of cyclins and cell cycle arrest at G0/G1 phase (Figs. 4–7; Supplementary Figs. S3–S8). Here, DDX3X is linked to neoplasm.