Importin-α proteins are required for transporting proteins from the cytoplasm into the nucleus via interaction with Importin-β in all tissues but also have roles in transcriptional regulation and organisation of chromatin and have been suggested to act as developmental switches during germline development. The Drosophila melanogaster genome encodes four Importin-α genes, also designated Karyopherin (Kap) genes. We have identified a specific requirement for Kap-α1 in maintenance of male germline stem cells and spermatogonial differentiation. Loss of function Kap-α1 mutants are male sterile. They lose germline stem cells (GSCs) and this loss can be rescued by germline specific expression of Kap-α1 but the rescued animals are still infertile indicating a secondary role of Kap-α1 in spermatogenesis. The GSC loss is accompanied by development of germ cell cysts that contain aberrant numbers of germ cells suggesting that cysts may be differentiating prematurely. The pre-meiotic Kap-α1 mutant phenotype can be phenocopied by germline expression of a dominant-negative Kap-α1 protein that lacks the Importin-β binding domain. We identified genes known to be expressed in the testis that produce proteins containing a consensus nuclear localisation sequence and screened for the ability of the dominant-negative allele to prevent protein transport into spermatogonial nuclei. From this screen we identified CycH and CG12909 as potential targets of Kap-α1. Germline specific knockdown of CG12909 produces a phenotype similar to that of Impα1 alleles. The mammalian ortholog of CG12909, LYAR, has been associated with recruitment of the methyltransferase PRMT5 to specific regions of chromatin and symmetric dimethylation of histone H4 Arg3. We are currently investigating if Kap-α1 mutants genetically interact with CG12909 or have defects in histone dimethylation.