Unexpectedly, when silencing RalGEF genes in lung cancer cells none of the Ras-dependant RalGEF stood out but one of the Ras-independent RalGEF did: RALGPS2 silencing produced the strongest inhibition of cell population growth among all six RalGEF in four NSCLC cell lines. Here, RALGPS2 is linked to non-small cell lung carcinoma.