znt

ZnT, short for zinc transporter, refers to the ZnT family of zinc transporter proteins encoded by the SLC30A gene family. ZnT proteins function to reduce cytosolic zinc levels by transporting Zn2+ into intracellular organelles or out of the cell, complementing the ZIP (SLC39) family that imports zinc into the cytosol. Together, ZnTs and ZIPs maintain zinc homeostasis essential for enzyme activity, signaling, and overall cellular health.

Most ZnT family members are integral membrane proteins featuring multiple transmembrane helices and cytosolic N- and C-termini, often with a histidine-rich loop. They typically operate as Zn2+-H+ antiporters, using the proton gradient to move zinc across membranes. This activity sequesters zinc in secretory organelles such as the Golgi apparatus and secretory vesicles or exports it to the extracellular space, thereby shaping zinc availability in different cellular compartments.

In mammals, there are about 10 ZnT proteins (ZnT1–ZnT10). Examples include ZnT1, which resides at the plasma membrane to export zinc; ZnT3, which loads zinc into synaptic vesicles; and ZnT8, located in insulin-containing secretory granules. ZnT5 and ZnT6 form functional pairs to deliver zinc to the Golgi and secretory pathway, while ZnT2 supplies zinc to secretory vesicles in mammary tissue. ZnT7 operates mainly in the Golgi, and ZnT9 is associated with the endoplasmic reticulum and Golgi; ZnT10 has been linked to manganese homeostasis, with potential indirect effects on zinc handling.

Clinical relevance has been shown for several ZnTs. Variants in SLC30A8 (ZnT8) influence type 2 diabetes risk and insulin secretion. Mutations in SLC30A2 (ZnT2) can cause neonatal zinc deficiency through impaired zinc provision in breast milk. Disruptions in ZnT function can affect immune, neural, and metabolic processes in various contexts.