Purpose of Review <p>Zinc (Zn) is essential for regulation of the hormones produced by pancreatic islets and for maintaining normal glucose homeostasis. The Zn transporter ZnT8, encoded by the <i>SLC30A8</i> gene, controls the accumulation of Zn in the insulin secretory granules of β-cells. This review synthesizes findings from human genetic studies and genetically modified animal models to clarify ZnT8’s role in type 2 diabetes (T2D) risk.</p> Recent Findings <p>ZnT8 loss of function impairs insulin crystallization and secretion and increases hepatic insulin clearance by reducing Zn-mediated inhibition of insulin degradation. Zn affects glucagon secretion from α-cells via paracrine signaling, though its in vivo role is still unclear. Both common risk alleles, such as rs13266634, and rare protective loss-of-function mutations in <i>SLC30A8</i> alter ZnT8 activity, which may influence T2D risk by affecting insulin dynamics and islet Zn handling.</p> Summary <p>Alterations in Zn homeostasis influence the pathogenesis of T2D primarily through ZnT8-mediated effects on insulin secretion and clearance. These findings suggest that targeted preventive strategies and genotype-guided Zn supplementation may offer novel approaches to reducing T2D risk, especially among high-risk individuals.</p>