Exploring the Healing Powers of Histatins: From Oral Health to Therapeutics.

Abstract

Histatin peptides are a family of small histidine-rich cationic polypeptides produced by two genes, HTN1 and HTN3. They are found in salivary secretions from the parotid, sublingual, and submandibular salivary glands. These peptides undergo proteolytic cleavages to produce different histatin fragments which play multiple roles including wound healing, maintenance of enamel, and regulation of balance in the oral microbiome. In this review, we explored the expression, structural characteristics, and metal-ion-binding capacities of these peptides and how their functions are modulated by their structure. We also provide here an insight into the potential use of histatins as biomarkers and therapeutic peptides in the management of oral and non-oral diseases including cancer. Potential gaps in the current understanding of histatins that warrant further research have also been highlighted. Copyright © 2025 by the authors.