Human tooth enamel, the most mineralized tissue in body, contains less than 2 wt% protein. Consequently, the importance of the protein to enamel mechanical response has always been overlooked. In this study, the role of minor protein in providing enamel microstructure and mechanical performance, especially tribological properties, were studied using deproteinization treatment and nano-indentation/scratch technique. Via the change from the original to the deproteinated conditions, a nanostructure degeneration from the assembly of hydroxyapatite (HA) crystals into nano-fibers to crystal aggregation has been found between the high-wearresistance and low-wear-resistance on the enamel surface. Correspondingly, an energy dissipation to cause a unit volume of wear on enamel surface decreases by 50%, and wear volume increases by 80%. With the presence of protein, the occurrence of enamel wear requires to break the interfacial protein bonding between the HA crystals in nano-fibers and the break dissipates considerable energy, which benefits the enamel to resist wear. Thus, the protein in enamel, although of a very low content, is essential to resisting wear by mediating the assembly of rigid HA crystals via interfacial protein bonding. Replicating functions of the protein component will be critical to the successful development of bio-inspired materials that are designed for wear-resistance.