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Using quantitative proteomics, we identified a previously unreported platelet zinc transporter, transmembrane protein 163 (TMEM163), which was significantly reduced in BLOC-1 (Dtnbp1sdy and Pldnpa)\u2013, BLOC-2 (Hps6ru)\u2013, or AP-3 (Ap3b1pe)\u2013deficient mice and HPS patients (HPS2, HPS3, HPS5, HPS6, or HPS9). We observed similar platelet DG defects and higher intracellular zinc accumulation in platelets of mice deficient in either TMEM163 or dysbindin (a BLOC-1 subunit). In addition, we discovered that BLOC-1 was required for the trafficking of TMEM163 to perinuclear DG and late endosome marker\u2013positive compartments (likely DG precursors) in MEG-01 cells. Our results suggest that TMEM163 is critical for DG biogenesis and that BLOC-1 is required for the trafficking of TMEM163 to putative DG precursors. These new findings suggest that loss of TMEM163 function results in disruption of intracellular zinc homeostasis and provide insights into the pathogenesis of HPS or platelet storage pool deficiency.<\/jats:p>","DOI":"10.1182\/blood.2020007389","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T22:05:28Z","timestamp":1611957928000},"page":"1804-1817","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":25,"title":["A zinc transporter, transmembrane protein 163, is critical for the biogenesis of platelet dense granules"],"prefix":"10.1182","volume":"137","author":[{"given":"Yefeng","family":"Yuan","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory for Genetics of Birth Defects\/Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Genetics and Birth Defects Control Center\/National Center for Children\u2019s Health, and Beijing Children\u2019s Hospital\/Capital Medical University, Beijing, China;"},{"name":"University of Chinese Academy of Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Dermatology, Beijing Tongren Hospital, Capital Medical University, Beijing, China;"},{"name":"Shunyi Women and Children\u2019s Hospital of Beijing Children\u2019s Hospital, Beijing, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiahe","family":"Huang","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanying","family":"Chen","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory for Genetics of Birth Defects\/Beijing Pediatric Research Institute, MOE Key Laboratory of Major Diseases in Children, Genetics and Birth Defects Control Center\/National Center for Children\u2019s Health, and Beijing Children\u2019s Hospital\/Capital Medical University, Beijing, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilin","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Li","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"University of Chinese Academy of Sciences, Institute of Genetics and 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