Hornerin (HRNR) is a filaggrin-like protein that functions as a structural component of epidermal cornified cell envelopes 1. In normal skin physiology, HRNR localizes to keratohyalin granules and corneocyte peripheries, where it undergoes post-translational modification through deimination and proteolytic processing by calpain-1, followed by cross-linking via transglutaminases to establish the skin barrier 2. HRNR expression is dynamically regulated during cornification, with altered expression patterns associated with atopic dermatitis and other hyperkeratotic conditions 3. Beyond its structural role, HRNR demonstrates antimicrobial properties through ribosome-targeting peptide sequences that accumulate intracellularly in bacteria and disrupt protein synthesis 4. Clinically, HRNR dysregulation is implicated in multiple pathologies. In hepatocellular carcinoma, HRNR overexpression promotes tumor progression through AKT pathway activation, correlating with poor disease-free and overall survival 5. Furthermore, circulating HRNR protein mediates immune evasion by stabilizing PD-L1 expression through mTORC1 signaling, potentially compromising anti-PD-L1 immunotherapy efficacy 6. HRNR amplification also occurs in sebaceous carcinomas 7. Interestingly, HRNR shows upregulation in Alzheimer's disease, though its functional significance remains unclear 8.