Ral GTPases in tumorigenesis: Emerging from the shadows

•The RalGEF-Ral pathway is a key effector pathway downstream of oncogenic Ras.•RalA and RalB exhibit distinct and redundant roles in tumorigenesis.•RalA and RalB activate a diverse set of effector pathways.•Ral GTPases potentially regulate several hallmarks of human cancer.

Oncogenic Ras proteins rely on a series of key effector pathways to drive the physiological changes that lead to tumorigenic growth. Of these effector pathways, the RalGEF pathway, which activates the two Ras-related GTPases RalA and RalB, remains the most poorly understood. This review will focus on key developments in our understanding of Ral biology, and will speculate on how aberrant activation of the multiple diverse Ral effector proteins might collectively contribute to oncogenic transformation and other aspects of tumor progression.