LCE3B (late cornified envelope 3B) is a structural protein component of the cornified envelope in the skin's stratum corneum that plays dual roles in barrier function and innate immunity 1. The protein exhibits defensin-like antimicrobial activity against both Gram-positive and Gram-negative bacteria at low micromolar concentrations, contributing to cutaneous host defense 1. A common deletion polymorphism affecting both LCE3B and LCE3C genes (LCE3C_LCE3B-del) is significantly associated with increased susceptibility to psoriasis across multiple ethnic populations, including Europeans and Asians, with odds ratios ranging from 1.21-1.27 23. This deletion also confers risk for psoriatic arthritis, particularly oligoarticular disease, and shows associations with rheumatoid arthritis and systemic lupus erythematosus in some populations 45. Interestingly, the LCE3C_LCE3B deletion leads to compensatory upregulation of the adjacent LCE3A gene, which also possesses antimicrobial properties 1. The genetic variant interacts epistatically with HLA-Cw6, another major psoriasis risk factor, highlighting the complex interplay between skin barrier integrity and immune system function in autoimmune skin diseases 3.