Cancer heterogeneity is a major obstacle for therapeutic development of treatment resistant prostate cancer. There is still much to be understood regarding epithelial tissue nuances and how cell-specific biology influences drug targets. In their study on page 33, Triscott and colleagues uncover an enrichment of the alpha isoform of the phosphatidylinositol-5-phosphate 4-kinase (PI5P4Kα) in the prostate basal cell layer. PI5P4Kα is a metabolic kinase that is implicated in supporting prostate cancer survival during conditions of treatment stress. The authors demonstrate that PI5P4Kα can be targeted to slow the progression of an aggressive basal cell-driven prostate cancer in a mouse model. The cover features an immunofluorescent image of a prostate from the mouse model, where eYFP-positive cells indicate active Crerecombinase targeting of basal epithelial cells. The eYFP is overlayed with a dual stain for cytokeratin 5 (CK5, red) that demonstrates positive basal lineage identification, and nuclei are in blue. This study is also highlighted on page 5.