Beyond calcium homeostasis: Vitamin D signaling in salivary gland biology and disease: Current evidence and emerging perspectives

Background Vitamin D is a pleiotropic secosteroid hormone that regulates numerous biological processes beyond calcium and phosphate homeostasis, including epithelial differentiation, immune function, oxidative stress responses, and tissue repair. These effects are mediated primarily through the vitamin D receptor (VDR), which is expressed across multiple cellular compartments of the salivary gland. Although researchers have extensively studied vitamin D in skeletal biology and mineralized oral tissues, its role in salivary gland physiology and pathology has received comparatively little attention. Highlight VDR signaling has been implicated in salivary gland homeostasis through effects on epithelial differentiation, antimicrobial defense, immune regulation, and secretory-cell integrity. Experimental studies further link VDR signaling to redox regulation and ferroptosis, and recent salivary gland-specific evidence indicates that its effects on cell survival and glandular function are context-dependent rather than uniformly protective. The vitamin D-VDR axis also regulates the salivary gland immune microenvironment by modulating antimicrobial peptide production and innate and adaptive immune responses. Current data implicate altered vitamin D signaling in several salivary gland disorders, including Sjögren syndrome, salivary gland tumors, and sialolithiasis, although most evidence comes from experimental studies and observational clinical investigations. In addition, vitamin D-related biomarkers, particularly vitamin D-binding protein, show potential for non-invasive assessment of oral and salivary gland health. Conclusion Collectively, these findings support a broader role for vitamin D signaling in salivary gland biology than previously recognized. Future studies that integrate systemic vitamin D status, local VDR activity, salivary biomarkers, and functional outcomes are needed to clarify the diagnostic, prognostic, and therapeutic relevance of this pathway in salivary gland disease.