ZnTs: Key Regulators of Zn²⁺ Homeostasis in Diseases

Zinc (Zn²⁺) is an essential trace element that plays a crucial role in various biological functions. Aberrant Zn²⁺ homeostasis may lead to the occurrence and development of diseases. Zinc transporters, primarily classified into two families in humans: the ZnT (SLC30A) family and the ZIP (SLC39A) family, are critical regulators of Zn²⁺ homeostasis. The roles of ZnT-mediated Zn²⁺ homeostasis in diseases are an active area of research. The ZnT family comprises ten members, belonging to four subfamilies, which are widely distributed in various tissues and subcellular organelles. ZnTs mediate directional Zn²⁺ efflux, transporting cytoplasmic Zn²⁺ into extracellular compartments or sequestering it within intracellular vesicles. Accumulating evidence has shown that ZnT dysregulation or ZnT mutations can disrupt Zn²⁺ homeostasis, leading to the occurrence and development of diseases, such as cancer, cardiovascular disease, and neurodegenerative diseases. In this review, we focus on the distribution and structure of ZnTs. Furthermore, we synthesize recent advances in ZnT-mediated regulation of Zn²⁺ homeostasis in disease pathogenesis to guide the development of novel diagnostic and therapeutic strategies.