RalBP1

Ral-binding protein 1, commonly abbreviated RalBP1 and also known as RLIP76, is a cytosolic protein that serves as an effector of the RalA and RalB GTPases. Encoded by the human RALBP1 gene, RLIP76 participates in signaling pathways that connect Ral activation to vesicle trafficking, endocytosis, and cytoskeletal dynamics.

RLIP76 contains distinct functional regions, including an N-terminal Ral-binding domain that binds the active, GTP-bound forms of RalA and RalB, a central RhoGAP domain capable of stimulating GTP hydrolysis by Rac1 and Cdc42, and a C-terminal region that interacts with components of the endocytic machinery such as AP2. Through these interactions, RalBP1 influences actin remodeling and clathrin-mediated endocytosis, integrating Ral signaling with membrane traffic and trafficking routes.

In addition to its signaling roles, RLIP76 functions as an ATP-dependent transporter for glutathione-conjugated electrophiles and certain chemotherapeutic drugs. This transport activity contributes to cellular detoxification and can influence cellular resistance to chemotherapy.

Regulation of RLIP76 occurs at the level of protein interactions and phosphorylation, and its localization and activity are responsive to cellular signaling cues that activate Ral GTPases. RLIP76 is widely expressed and has been implicated in various cellular processes, including migration and survival.

Clinical and research interest centers on RLIP76’s role in cancer biology, where its overexpression has been linked to tumor progression and drug resistance. Consequently, RalBP1/RLIP76 is studied as a potential target for therapeutic intervention in certain cancers.