HTN1 (histatin 1) is a salivary antimicrobial peptide with pleiotropic functions in wound healing and immune defense. Primary function: HTN1 promotes cell migration and wound healing in oral and non-oral tissues, including keratinocytes, fibroblasts, and endothelial cells, thereby accelerating re-epithelialization and angiogenic responses 1. Mechanism: HTN1 is internalized into host cells and targets mitochondria and endoplasmic reticulum to promote metabolic activity and cell migration via ERK1/2 signaling pathway activation [UniProt sources]. The peptide also mediates antimicrobial humoral immune responses and coordinates with IL-17/IL-22-producing T cells for antimicrobial peptide expression in mucosal defense 2. Disease relevance: HTN1 expression is dysregulated in allergic fungal rhinosinusitis (AFRS), where severely downregulated HTN1 correlates with deficient antifungal activity and impaired STAT3-dependent TH17/TH22 differentiation 2. HTN1 expression is also elevated in advanced head and neck squamous cell carcinoma and associates with tumor progression and metastasis 3. Clinical significance: Therapeutic approaches enhancing HTN1 and antimicrobial peptide production may benefit AFRS patients and warrant evaluation in immunocompromised conditions affecting mucosal immunity.