Two members of the family of Ras-like small GTPases, RalA and RalB (EC 3.6.5.2), act downstream of Ras in the Ral guanine nucleotide exchange factor (RalGEF)/Ral GTPase pathway, and activate cellular processes through effectors, including Ral-binding protein 1 (RALBP1; also known as RLIP76 and RIP1), the human exocyst subunits SEC5 and EXO84, filamin and phospholipase D1. These effectors mediate regulation of cell adhesion (anchorage independence), membrane trafficking (exocytosis and endocytosis), mitochondrial fission, and transcription. RalA and RalB are important drivers of the proliferation, survival and metastasis of multiple human cancers, including skin, lung, pancreatic, colon, prostate, and bladder cancers[1].