In most adult tissues homeostasis is maintained by tight regulation and crosstalk between pathways controlling self-renewal versus differentiation in adult Somatic Stem cells (SSC). Misregulation of signaling pathways regulating these processes have been linked to several conditions, such as cancer, and other age related diseases. In the last decade SSC in the Drosophila melanogaster intestinal epithelium have emerged as a powerful model to study these mechanisms. In this simple tissue the intestinal lineage has been well characterized and markers for every cell population have been defined. Recently our laboratory has identified zinc-finger homeodomain 2 (zfh2), a highly conserved transcription factor, as an important player in the maintenance of intestinal homeostasis. Using immunohistochemistry, I have shown that zfh2 is expressed in the Drosophila intestinal progenitors. Interestingly zfh2 over-expression leads to a mild hyperproliferation phenotype. Conversely, its knock-down completely blocks stress mediated proliferation. Our preliminary data suggests that zfh2 knock-down does not affect basal tissue turnover. In conclusion I have shown that proper expression of zfh2 is necessary to maintain tissue homeostasis in the Drosophila melanogaster intestinal epithelium. We are now testing interactions with pathways known to regulate intestinal stem cell proliferation. Interestingly, mutations in ATBF1, the zfh2 mammalian homolog, have been associated with different types of cancers. However nothing is known about any possible role of ATBF1 in adult tissues under basal conditions. Characterizing zfh2 in the Drosophila adult intestinal epithelium can shed light on the function of its mammalian homolog.