LCE2D (late cornified envelope 2D) encodes a precursor protein of the cornified envelope in the stratum corneum, the outermost layer of the epidermis. As a structural component of the skin barrier, LCE2D functions through protein binding interactions to contribute to skin integrity and differentiation. 1 LCE2D serves as a reliable skin-specific RNA biomarker for forensic tissue identification. In collaborative studies, LCE2D was successfully incorporated into a skin1 pentaplex panel alongside LCE1C, IL1F7, and CCL27 to identify skin samples and contact traces from various sources including fingerprints, clothing, and electronic devices. 1 The simultaneous detection of LCE2D mRNA with DNA profiling enables positive identification of tissue origin while maintaining compatibility with current STR typing technology for donor identification. Clinically, LCE2D has emerged as a potential biomarker in cancer biology. In head and neck squamous cell carcinoma (HNSCC), LCE2D was identified as one of ten hub genes showing differential expression patterns associated with significantly decreased patient survival. 2 These findings suggest that genomic alterations and altered expression of LCE2D warrant investigation for early diagnosis, prognostic assessment, and potential targeted therapeutic approaches in HNSCC. Overall, LCE2D represents both a fundamental skin barrier component and an emerging molecular marker relevant to forensic biology and oncology.