LCE3D (late cornified envelope 3D) is a structural protein component of the cornified envelope in the stratum corneum, serving as a precursor for skin barrier formation 1. The gene functions in keratinocyte differentiation and plays a role in maintaining epidermal integrity. LCE3D is recognized as a psoriasis susceptibility locus identified through genome-wide association studies across multiple ethnic populations 23. A specific polymorphism (rs4085613) in LCE3D is associated with treatment response to brodalumab therapy in plaque psoriasis, with certain genotypes conferring reduced probability of achieving optimal clinical response 4. The gene has been identified as a candidate biomarker for predicting psoriasis disease severity 5. Beyond psoriasis, LCE3D expression is upregulated following solar protection and repair strategies in reconstructed human skin models, suggesting involvement in photoprotection and UV-damage repair mechanisms 1. Recent transcriptome-wide association studies identified LCE3D as a hub gene orchestrating keratinization pathways in atopic dermatitis, positioning it as a potential drug target 6. The gene also shows altered expression in head and neck squamous cell carcinoma 7. These findings collectively indicate LCE3D's importance in skin barrier function, disease susceptibility, and potential therapeutic targeting across multiple dermatological and malignant conditions.