Cellular and mechanistic studies indicate that RALB associates with DR5 and the death-inducing signalling complex (DISC) in a ligand-dependent manner, and that inhibition of RALB combined with DR5 agonists can be a novel treatment strategy for poor prognostic Colorectal Cancer Intrinsic Subtype (CRIS)-B13KRASMT CRC. Here, RALB is linked to colorectal carcinoma.