Hydrogen Sulfide Pathways and Zinc-Containing Proteins in Human Diseases: A Systematic Review and Evidence Map

Hydrogen sulfide can regulate protein function, but interactions with zinc-containing proteins and their relevance to human disease remain uncertain. We assessed recent human evidence linking sulfur exposure or endogenous sulfur-pathway alterations to zinc-containing proteins and disease-associated outcomes. Article eligibility covered the last five years: 2021–2026. PubMed and ScienceDirect records were searched. Human findings were classified by protein target, zinc function, measured endpoint and mechanistic attribution. The assessed reports described modification-sensitive signals, gene expression, protein abundance and localization involving epigenetic regulators, metalloproteinases, alkaline phosphatase, superoxide dismutase and metallothioneins. Bone-specific alkaline phosphatase concentration increased following uncontrolled sulfurous-water inhalation, whereas total alkaline phosphatase activity showed no significant change. Descriptive co-profiling did not establish sulfur-dependent protein regulation. No assessed human report demonstrated direct sulfide coordination at protein-bound zinc or zinc-site-mediated clinical benefit. Differences in study designs, exposures and endpoints did not support quantitative pooling of the assessed findings. Recent human findings identify candidate sulfur–protein relationships whose functional and therapeutic relevance requires validation. Progress depends on chemically specific exposure measurements, target-specific functional assays and controlled clinical outcomes. Systematic Review Registration: PROSPERO CRD420261535243.