SLC39A4 encodes ZIP4, a selective zinc transporter that plays an essential role in dietary zinc uptake from the small intestine 1. The protein mediates Zn2+ transport across cell membranes and exhibits zinc-dependent regulation of its uniporter activity 1. ZIP4 is highly expressed in the duodenum and jejunum, where it transports dietary zinc ions from the intestinal lumen into enterocytes 2. Beyond zinc homeostasis, ZIP4 functions as a cancer-promoting factor by activating EMT plasticity through the miR-373-LATS2-ZEB1/YAP1-ITGA3 signaling axis in pancreatic cancer 3. In glioblastoma, ZIP4 modulates microglial plasticity through extracellular vesicles carrying TREM1, promoting a protumorigenic immune environment 4. Mutations in SLC39A4 cause acrodermatitis enteropathica (AE), a rare autosomal recessive disorder characterized by periorificial dermatitis, alopecia, and diarrhea due to impaired zinc absorption 52. Clinical manifestations can occur even with normal serum zinc levels, making alkaline phosphatase a valuable diagnostic marker 6. The mutational spectrum is diverse, with over 31 variants reported across the entire gene 2. Treatment involves zinc supplementation, which is crucial for immune function and intestinal adaptation 78.