Overexpression of PPAR-alpha, a developmental transcription factor important in epidermal embryogenesis, in basal keratinocytes causes epidermal thinning when activated constitutively during development, but not if activated in adults; and lack of PPAR-alpha transiently delays stratum corneum formation within a window late in epidermal development (day 18.5 to birth). In contrast, pharmacologic activation of PPAR-alpha inhibits proliferation and induces differentiation in mouse epidermis regardless of developmental stage. Thus, PPAR-alpha is an important regulator of epidermal homeostasis.