Psoriasis is the most common inflammatory skin disease affecting 1-3% of the world’s population. Both keratinocyte cells and immune cells are central in the disease pathogenesis. The Marinkovich Lab at Stanford University has established that psoriatic keratinocytes have an intrinsic predisposition for Rac1 hyperactivation. Rac1 is a small GTPase known to regulate many important cellular processes, including those mediating cell cytoskeletal rearrangements, cellular migration, cell-cell adhesion, and the cell cycle. Through ectopic overexpression of mutant hyperactive V12Rac1 in keratinocytes, we can induce phenotypes closely resembling human psoriasis through stimulation with psoriatic immune cells or inflammatory cytokines both in vivo and in vitro. It is known that psoriatic epidermis has a marked increase of proliferating cells that abnormally extends into suprabasal layers of the epidermis. Furthermore, cells in the suprabasal layers of psoriatic epidermis express proteins that are only normally expressed in basal keratinocytes, indicating that there is an increased number of cells in a more progenitor-like state in psoriatic skin. This is of interest because previous studies have demonstrated that Rac1 is necessary for maintenance of epidermal stem cells. One key protein that regulates keratinocyte differentiation is p63, and we hypothesize that there may be abnormalities of p63 expression or function in psoriatic epidermis with hyperactive Rac1, causing a delay in differentiation of psoriatic keratinocytes. To study p63, V12Rac1 is ectopically expressed in keratinocytes to prime a psoriatic signaling cascade that, upon proinflammatory cytokine stimulation, will enable us to elucidate what may be occurring with p63 expression and function in psoriatic epidermis, and unravel how hyperactive Rac1 may perturb psoriatic keratinocyte differentiation and proliferation.