Table 1 ZnT proteins- expression and physiological roles.

ZnT-1

Ubiquitous

Plasma membrane

Overexpression: reduced [Zn²⁺] _i and enhanced resistance against Zn²+ toxicity, KO: Lethal at embryonic stage,

(37,42,43,71)

ZnT-2

small intestine, kidney, placenta, pancreas, testis, seminal vesicles, and mammary gland

Vesicles, lysosomes

Overexpression: enhanced lysosomal and vesicular Zn²⁺ accumulation

(72,73)

ZnT-3

brain

Synaptic vesicles (Glutamatergic and GABAergic)

KO: synaptic Zn²⁺ deficiency, enhanced susceptibility to seizure, loss of gender specific Alzheimer’s disease plaque formation in a mouse model, decreased susceptibility to amyloid angiopathy

(49,74)

ZnT-4

mammary gland, brain, small intestine and mast cells

Intracellular compartments

Lethal milk syndrome in mice, Asthma (mice), Alzheimer’s disease

(75–79)

ZnT-5

Pancreatic β-cells, intestine, heart brain, liver, kidney

Insulin secretory vesicles, Golgi Spliced isoform: plasma membrane Complexed with ZnT-6

KO: poor growth, osteopenia, male specific fatal arrhythmias. Essential for folding and secretion of Zn²⁺ -binding enzymes.

(53–55,59,80)

ZnT-6

liver, brain, and small Intestine

Complexed with ZnT-5

Alzheimer’s disease (mice)

(53,57,79)

ZnT-7

small intestine, liver, retina, spleen, kidney, and lung

Golgi

Essential for folding and secretion of Zn²⁺ -binding enzymes,

(54,81,82)

ZnT-8

Pancreatic β-cells

Insulin secretory vesicles

Polymorphism marker in diabetes type II

Overexpression: enhances glucose dependent insulin secretion

(60–62)