Tooth enamel is the hardest tissue in the human body with a complex hierarchical structure. Enamel hypomineralisation--a developmental defect--has been reported to cause a marked reduction in the mechanical properties of enamel and loss of dental function. We discover a distinctive difference in the inelastic deformation mechanism between sound and hypomineralised enamels that is apparently controlled by microstructural variation. For sound enamel, when subjected to mechanical forces the controlling deformation mechanism was distributed shearing within nanometre thick protein layer between its constituent mineral crystals; whereas for hypomineralised enamel microcracking and subsequent crack growth were more evident in its less densely packed microstructure. We develop a mechanical model that not only identifies the critical parameters, i.e., the thickness and shear properties of enamels, that regulate the mechanical behaviour of enamel, but also explains the degradation of hypomineralised enamel as manifested by its lower resistance to deformation and propensity for catastrophic failure. With support of experimental data, we conclude that for sound enamel an optimal microstructure has been developed that endows enamel with remarkable structural integrity for durable mechanical function.