LCE3A is a structural protein of the stratum corneum that functions as an antimicrobial component of innate cutaneous host defense 1. The protein possesses defensin-like antimicrobial activity against a broad spectrum of Gram-positive and Gram-negative bacteria at low micromolar concentrations 1. LCE3A expression is upregulated in individuals carrying the psoriasis-associated LCE3B/C deletion, a compensatory response that may partially mitigate the loss of these adjacent genes 1. The expression of LCE3A is regulated through STAT3-dependent signaling at an enhancer region, with this regulation showing epistatic interaction with the major psoriasis risk allele HLA-Cw6 2. In vivo, LCE3A contributes to shaping cutaneous and oral microbiota composition; genetic variations affecting LCE3A expression correlate with altered microbiota diversity 3. Upon inflammation, LCE3A may regulate skin barrier repair by modulating bacterial colonization and immune responses to bacterial antigens 1. LCE3A expression can be therapeutically induced through vitamin D receptor ligands including 1,25-dihydroxyvitamin D3, curcumin, and docosahexaenoic acid, suggesting a mechanism for psoriasis treatment 4 5. Genetic variants near LCE3A show stronger association with cutaneous-only psoriasis than psoriatic arthritis 6.