Since inhibition of Wnt signaling prevents gland formation, it has been difficult to determine the functional role of Wnt signaling in later and adult stages of mammary gland development. Wnt signaling has been shown to be important not only to the maintenance of stem/progenitor compartments in gut, but in a number of other cell lineages. These include hematopoetic and embryonic stem cells. Specifically, several compo-nents of the canonical Wnt signaling pathway have been found to be expressed in both embryonic and hematopoetic stem cell populations. Moreover,CPI-613 treatment with Wnt ligands or down-stream activation of the Wnt signaling pathway inhibits differentiation and promotes self-renewal of these cells. Studies published in 2006 showed that subpopulations of basal mammary cells could be isolated from the total population, that show enhanced regenerative capacity when assayed in vivo. A single cell from this population was sufficient to recreate a whole gland, and they were coined somatic mammary stem cells. These subpopulations are separated by their high expression of both CD24 and CD49f, but their purity is unlikely to be higher than 5%. Neither of these markers alone is useful for the identification of stem cells,CUDC-907 or indeed resolution of whole mammary epithelial cell populations. Therefore, the behavior of the cells that are key to the growth or regeneration of glands has not yet been described. It has become a high priority to find a molecule that is a specific marker of stem cell function, for their evaluation during normal and pathogenic development. Previously, we showed that Lrp5 null mammary glands, though grossly normal, were remarkably resistant to Wnt1-induced tumor development. This resis-tance occurred despite the presence of Lrp6, and served to focus our attention on the specific functions of Lrp5. Lrp5 null glands were almost devoid of regenerative potential when tested by in vivo stem cell assay. Here, we show that both Lrp5 and-6 proteins are expressed in the basal epithelial cell population. We also show that the loss of Lrp5 does not significantly affect the response of cultured mammary epithelial cells, tested with an in vitro Wnt reporter assay.