TMEM163 is a zinc efflux transporter belonging to the cation diffusion facilitator (CDF) protein superfamily that mediates cellular zinc homeostasis 1. The protein binds divalent cations including Zn²⁺, Ni²⁺, and minor amounts of Cu²⁺, functioning as a zinc effluxer through conserved aspartate residues (D124/D128) critical for transport activity 1. TMEM163 localizes to the plasma membrane, lysosomes, early endosomes, and synaptic vesicles, where it forms both homodimers and functionally relevant heterodimers with ZNT family members (ZNT1-4) 2. Beyond zinc transport, TMEM163 serves as a functional modulator of P2X purinoceptors 3 and plays essential roles in CNS development, myelination, and oligodendrocyte survival and proliferation 4. TMEM163 is critical for platelet dense granule biogenesis through BLOC-1-mediated trafficking to lysosomal compartments 5. De novo heterozygous variants (L76R/L76P) in TMEM163 cause hypomyelinating leukodystrophy, with zebrafish models demonstrating that tmem163 loss results in myelin deficiency, neuronal loss, and oligodendrocyte apoptosis 4. Additionally, TMEM163 variants are associated with Parkinson disease susceptibility 6 and PBC prognosis 7, indicating broader pathophysiological relevance.