Cryptococcus neoformans is a ubiquitous environmental human fungal pathogen that claims 180,000+ lives annually. There is only one approved treatment regimen, which requires expensive facilities, equipment, and toxic drugs for at least three months to one year. Previously, we demonstrated that zinc finger 2 transcription factor gene overexpressing (ZNF2oe) Cryptococcus cells are nonvirulent. We also discovered that cellular components present in ZNF2oe cells are immunogenic and protective. Because Znf2 regulates half of the glycophosphatidyl inositol (GPI)-anchored mannoproteins encoded by the H99 genome and mannoproteins are likely antigens present in the cell wall or the capsule, we focused on the characterization of these GPI-anchored mannoproteins in this study. Our research reveals ZNF2oe increases surface antigen presentation, ZNF2oe host-protective responses require capsule polysaccharide, the identification of 29 candidate host-protective GPI-mannoproteins, and three tools to further investigate GPI-mannoproteins as targets for developing a Cryptococcus-specific or universal fungal vaccine.