Zinc transporter ZIP9 (ZIP9)

Zinc transporter ZIP9 is a multifunctional transmembrane protein encoded by the SLC39A9 gene, notable for its dual role as a zinc transporter and a membrane androgen receptor (mAR). Unlike classical nuclear androgen receptors, ZIP9 is located at the plasma membrane and mediates rapid, non-genomic androgen signaling through G protein coupling, regulating intracellular zinc concentrations and triggering downstream effects including apoptosis and tight junction formation. ZIP9 is widely expressed across tissues, with increased expression in certain cancers such as breast and prostate cancer. It has high affinity for testosterone but low affinity for other androgens, and can be antagonized by bicalutamide. ZIP9 is considered a promising therapeutic target, particularly in hormonally driven cancers and reproductive health, though broad tissue expression presents therapeutic challenges[1][2][3][4][7].

Other names

Membrane androgen receptor ZIP9Solute carrier family 39 member 9SLC39A9mAR (membrane androgen receptor) ZIP9

Agonists (e.g., testosterone) bind ZIP9 at the plasma membrane, activating G protein–coupled signaling (Gs or Gi, context dependent) that influences second messenger pathways and elevates intracellular zinc, ultimately inducing apoptosis or regulating tight junctions[1][2][3][4]. Antagonists (e.g., bicalutamide) block androgen binding and subsequent signaling transduction[2].