Lumican regulates collagenous matrix assembly as a keratan sulfate proteoglycan in the cornea and is also present in the connective tissues of other organs and embryonic corneal stroma as a glycoprotein. In normal unwounded cornea, lumican is expressed by stromal keratocytes. Interestingly, injured mouse corneal epithelium ectopically and transiently expresses lumican during the early phase of wound healing, suggesting a potential lumican functionality unrelated to regulation of collagen fibrillogenesis, e.g., modulation of epithelial cell adhesion or migration. Healing of a corneal epithelial injury in lumican knockout (Lum–/–) mice was significantly delayed compared with Lum+/– mice. Addition of purified lumican to cultured medium promoted re-epithelialization and enhanced cell proliferation of wild-type mouse corneal epithelial cells in an organ culture. Therefore, administration of lumican may be beneficial for treating epithelial defects in the cornea and other tissues.