The atypical kinase C (aPKC) is a central coordinator of cell polarity. Previously, our laboratory has identified a key role for the mammalian aPKCl in balancing epidermal stem cell renewal and differentiation. Loss of aPKCl in the epidermis resulted in a loss of stem cells and increased differentiation, as well as cell shape changes, ultimately resulting in premature skin aging. To address the underlying mechanisms by which aPKC control cell shape and cell fate alterations we combined knockout primary cells, multi-layered proteomics and bioinformatics. Integrating the interactome and phosphoproteome datasets identified aPKCs as central coordinators of the cytoskeleton, cell-cell and cell-matrix junctions, including a previously unrecognized role for aPKC in keratin-associated desmosomes and hemidesmosomes. Functionally, aPKC regulates the cellular organization of the actin and keratin cytoskeleton as well as the force balance between cell-cell junctions and cell-matrix junctions. Spatiotemporal coordination of these antagonist activities drives epidermal delamination and differentiation as loss of aPKC or mutation of a single aPKC phospho-site in desmoglein-3 altered suprabasal positioning of cells. Thus, aPKCs are central organizers of cell- and tissue architecture, including desmosomal and keratin filament organization, and show that aPKC-dependent junctional dynamics is essential for proper tissue organization in the skin.