SLC39A5 is a zinc transporter that mediates zinc influx across the plasma membrane, particularly in intestinal, pancreatic, and ocular tissues 1. The protein functions as a saturable, temperature- and concentration-dependent uniporter that regulates intracellular zinc homeostasis and participates in transepithelial zinc transport 1. Beyond zinc transport, SLC39A5 regulates multiple signaling pathways: it modulates TGF-β signaling through zinc-dependent Smad stabilization, affecting extracellular matrix synthesis critical for ocular development 2; it influences glucose homeostasis through IL-6/STAT3-mediated suppression of glucagon secretion in pancreatic α-cells 3; and it activates PI3K/AKT and BATF-dependent pathways in cancer cells 45. Clinically, SLC39A5 mutations cause autosomal dominant myopia 24, with dysfunction impairing extracellular matrix synthesis in the sclera 26. SLC39A5 variants also associate with human height variation 7 and show protective effects against type 2 diabetes when inactivated 8. Additionally, SLC39A5 upregulation in gastric and lung cancers promotes malignant progression, suggesting therapeutic targeting potential 45. Zinc supplementation enhances intestinal adaptation in short bowel syndrome through SLC39A5-mediated pathways 1.