Ras-related protein Ral-A and Ras-related protein Ral-B (RalA and RalB) (RalA and RalB)

Ras-related protein Ral-A (RalA) and Ras-related protein Ral-B (RalB) are small GTPases of the Ras superfamily that serve as critical downstream effectors of Ras signaling. In the context of lung cancer, particularly KRAS-mutant non-small cell lung cancer (NSCLC), the Ral signaling pathway is frequently overactivated and drives tumor growth, survival, and metastasis. These proteins function as molecular switches, cycling between an active GTP-bound state and an inactive GDP-bound state to regulate diverse cellular processes such as vesicle trafficking, cytoskeletal organization, and mitochondrial fission. RalA is primarily associated with anchorage-independent growth and tumorigenesis, while RalB is often linked to cell survival, motility, and the innate immune response. Therapeutic targeting of these proteins has focused on small-molecule inhibitors that allosterically bind the GDP-bound form to prevent interaction with effectors such as RalBP1 (RLIP76) and the exocyst complex. Although no Ral-targeted drugs are currently FDA-approved, they represent a significant area of research for overcoming resistance in Ras-driven malignancies and addressing previously undruggable oncogenic pathways.

Other names

RALARALBRal GTPasesRas-like protein ARas-like protein BRas-related protein Ral-ARas-related protein Ral-B

Allosteric inhibition of the GDP-bound form of Ral GTPases to prevent effector binding and downstream signaling activation.