In both Drosophila and mammals, IkappaB kinases (IKKs) regulate the activity of Rel/NF-kappaB transcription factors by targeting their inhibitory partner proteins, IkappaBs, for degradation. We identified mutations in ik2, the gene that encodes one of two Drosophila IKKs, and found that the gene is essential for viability. During oogenesis, ik2 is required in an NF-kappaB-independent process that is essential for the localization of oskar and gurken mRNAs; as a result, females that lack ik2 in the germline produce embryos that are both bicaudal and ventralized. The abnormal RNA localization in ik2 mutant oocytes can be attributed to defects in the organization of microtubule minus-ends. In addition, both mutant oocytes and mutant escaper adults have abnormalities in the organization of the actin cytoskeleton. These data suggest that this IkappaB kinase has an NF-kappaB-independent role in mRNA localization and helps to link microtubule minus-ends to the oocyte cortex, a novel function of the IKK family.