HTN3 (histatin 3) encodes a salivary antimicrobial peptide whose primary product is histatin 5 (Hst 5), a major component with potent antifungal and antibacterial activities 1. Hst 5 functions through a multi-step mechanism: it binds C. albicans cell wall proteins SSA1 and SSA2, is internalized via fungal polyamine transporters DUR3 and DUR31, and targets mitochondria to induce reactive oxygen species formation and ATP release, ultimately causing fungal cell death 1. The peptide also inhibits the C. albicans TRK1 potassium transporter, causing osmotic imbalance and cell death, while simultaneously inhibiting bacterial proteases from P. gingivalis and human metalloproteases MMP2 and MMP9 1. Metal binding (zinc, copper, nickel) enhances enamel protection and antimicrobial activity through ROS formation and membrane disruption 1. HTN3 serves as a saliva-specific genetic marker for body fluid identification in forensic applications 2. Clinically, HTN3 shows disease relevance in salivary gland dysfunction conditions including Sjögren's syndrome, where adequate salivary secretion and histatin expression are compromised 1. Additionally, HTN3::MSANTD3 gene fusion has been identified as a recurrent molecular alteration in acinic cell carcinoma of salivary glands, offering potential diagnostic and prognostic utility 3.