Zinc (Zn) is an important micronutrient in the human body, and health complications associated with insufficient dietary intake of Zn can be overcome by increasing the bioavailable concentrations in edible parts of crops (biofortification). Wheat (Triticum aestivum L) is the most consumed cereal crop in the world; therefore, it is an excellent target for Zn biofortification programs. Knowledge of the physiological and molecular processes that regulate Zn concentration in the wheat grain is restricted, inhibiting the success of genetic Zn biofortification programs. This review helps break this nexus by advancing understanding of those processes, including speciation regulated uptake, root to shoot transport, remobilisation, grain loading and distribution of Zn in wheat grain. Furthermore, new insights to genetic Zn biofortification of wheat are discussed, and where data are limited, we draw upon information for other cereals and Fe distribution. We identify the loading and distribution of Zn in grain as major bottlenecks for biofortification, recognising anatomical barriers in the vascular region at the base of the grain, and physiological and molecular restrictions localised in the crease region as major limitations. Movement of Zn from the endosperm cavity into the modified aleurone, aleurone and then to the endosperm is mainly regulated by ZIP and YSL transporters. Zn complexation with phytic acid in the aleurone limits Zn mobility into the endosperm. These insights, together with synchrotron‐X‐ray‐fluorescence microscopy, support the hypothesis that a focus on the mechanisms of Zn loading into the grain will provide new opportunities for Zn biofortification of wheat.

Wheat contains low grain zinc (Zn) due to its genetics and the physiochemical properties of the soil in which it is grown. Consequently, where wheat forms a major part of the human diet, bioavailable Zn is below dietary requirements. Understanding the regulation of genes responsible for cellular Zn-transport, particularly those responsible for the control of the biosynthesis pathway of nicotianamine, provides an opportunity to increase Zn loading into the grain. Decreasing the levels of phytic acid, an inhibitor of Zn absorption in humans, provides another opportunity to increase the bioavailability of grain Zn. Synchrotron X-ray fluorescence microscopy clearly demonstrated that the crease region of the wheat grain is a major bottleneck to Zn loading in the endosperm. Higher expression of Zn transporter families, particularly metal tolerance proteins and yellow stripe like transporter families in the aleurone layer are also likely to play a major role in determining grain Zn content. Finally, anatomical barriers in the vascular region at the base of the wheat grain are a major limitation to Zn loading. Modification of any of these traits through traditional plant breeding or gene editing provides an opportunity to increase the Zn concentration in wheat grain.