The absence of Lrp5 generates a selective loss of the basal cell population, though the function of mammary glands is entirely preserved. Furthermore, the cells tend to become senescent in culture. In addition, we find that cells expressing high levels of Lrp5 co-localize with the CD24/CD49f double-positive stem cell-enriched fraction and have enhanced stem cell function in vivo. Previously, we have shown that Wnt1-induced, hyperplastic mammary glands accumulate undifferentiated cells and ductal regenerative/stem cells. Here, we show an increased proportion of basal cells and increased expression of a basal cell-associated p63 variant, DNp63,Carfilzomib associated with proliferative function in basal cell lineages. These glands subsequently develop solitary differentiated tumors with multiple lineage characteristics. We show here that loss of Lrp5 generates the reciprocal phenotype – slower ductal outgrowth, the accumulation of peri-senescent cells, almost total depletion of adult regenerative cells from the ductal tree, a reduced proportion of basal cells compared to luminal, and increased expression of the TAp63 isoform, associated with senescence. We predict that these glands will be highly tumor resistant. We have shown that Lrp5 is expressed together with Lrp6 on most/all basal cells of the mammary gland. However,CHIR-99021 most basal cells have a low cell surface expression of Lrp5, and only cells with a high level have enriched stem cell function. This fraction includes 80% of the mammary stem cells. Lrp5 is unique amongst the markers described so far for mammary epithelial populations for providing significant levels of stem cell enrichment without combining it with other markers. Wnt1-induced mouse mammary tumors share a transcriptional signature with Brca1+/2 and carcinogen-induced tumors, and these in turn share components of their basaloid signature with human basaloid tumors. Characteristically, all of these tumors have residual basal cells, and are likely to derive from the basal lineage. It is perhaps not surprising then that the key components of the oncogenic Wnt signaling pathway are specifically expressed by basal cells.