SLC39A6 is a zinc-influx transporter mediating cellular zinc homeostasis and playing a critical role in epithelial-to-mesenchymal transition (EMT). When forming a heterodimer with SLC39A10, SLC39A6 mediates zinc uptake that inactivates GSK3B, allowing SNAI1-mediated downregulation of adherence genes like CDH1 and promoting loss of cell adhesion 1. The SLC39A10-SLC39A6 heterodimer also initiates mitosis by importing zinc to trigger mitotic pathways 2. Beyond EMT, SLC39A6 participates in T-cell receptor signaling by mediating zinc uptake in activated lymphocytes 3 and regulates zinc influx necessary for oocyte meiotic progression 4. Clinically, SLC39A6 is significantly upregulated across multiple cancer types including breast, esophageal, gastric, colorectal, and liver cancers 56789. High SLC39A6 expression correlates with poor overall survival in esophageal, gastric, and liver cancers, and serves as an independent prognostic factor 678. Notably, in estrogen receptor-positive luminal breast cancer, high SLC39A6 expression associates with better prognosis 10. SLC39A6 is identified as an anoikis-related gene critical for breast cancer metastatic colonization 11. SLC39A6 represents a validated therapeutic target, with antibody-drug conjugates targeting this transporter showing cytotoxic activity in preclinical models 59.