Anti-fungal proteins (AFPs) of the plant defensin class are known to control Verticillium and Fusarium pathogens when assessed in vitro. Bioinformatics analyses of AFPs demonstrated that these small (~5 kDa) cystein-rich (6-8 residues) endogenous plant proteins may be members of a phylogenetically diverse class of structurally related proteins which share a scorpion-fold motif. AFPs may exert their inhibitory effects on fungal hyphae by utilizing the same strategy as scorpion toxins which perturb neuron function by interacting with gated channel proteins. To investigate this possibility, a series of experiments traditionally used to classify scorpion toxin function, based on interactions with different types of neural channel proteins, was conducted to evaluate whether AFPs act like 'scorpion defensins'. Perturbations of neural viability, steady-state electro-membrane potentials and sodium, potassium and calcium channel function were examined and compared using purified AFP proteins, scorpion toxin proteins, control neuro-toxins, and bovine serum albumin (BSA). AFPs are also homologous to plant 'sweet proteins' that may interact directly with taste receptors. Further evaluation of AFPs and sweet proteins showed high levels of stability in models of gastro-intestinal digestion. While stability may be important for sweet protein functionality, stability may also correlate with potential food allergenicity or toxicity. To assess potential allergenicity, a structural homologue of our AFPs was purified from wheat (gamma-thionin) and directly tested for allergenicity using IgE from wheat-allergic patients. In addition, acute oral toxicity studies of sweet proteins in mice demonstrated a lack of toxic effect at high doses. Data from these experiments are being used to direct new inquiries into the safety and function of plant AFPs and sweet proteins.