{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nThe studies collectively characterize TMEM165—a Golgi-resident Ca2⁺/H⁺ antiporter—as a key regulator of Golgi ion homeostasis in diverse physiologic contexts. In lactating mammary tissue, TMEM165 is markedly upregulated at the onset and peak of lactation, suggesting it complements the Ca2⁺ pumps SPCA1 and SPCA2 by mediating calcium transport through the Golgi to support the high secretory demands of milk production. Rapid declines in its expression during involution further underscore its role during active lactation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel, TMEM165 loss of function in skeletal cells has been shown to disrupt Mn2⁺ homeostasis in the Golgi, leading to an impaired elongation of chondroitin- and heparan-sulfate glycosaminoglycan chains. This defect compromises proteoglycan synthesis, disturbs TGFβ and BMP signaling pathways, and accelerates chondrocyte maturation, thereby contributing to severe skeletal dysplasia and dwarfism—a phenotype that can be ameliorated by Mn2⁺ supplementation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Timothy A Reinhardt, John D Lippolis, Randy E Sacco "}, {"type": "b", "children": [{"type": "t", "text": "The Ca(2+)/H(+) antiporter TMEM165 expression, localization in the developing, lactating and involuting mammary gland parallels the secretory pathway Ca(2+) ATPase (SPCA1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2014.02.020"}], "href": "https://doi.org/10.1016/j.bbrc.2014.02.020"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24530912"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24530912"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Sajida Khan, Malak Sbeity, François Foulquier, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM165 a new player in proteoglycan synthesis: loss of TMEM165 impairs elongation of chondroitin- and heparan-sulfate glycosaminoglycan chains of proteoglycans and triggers early chondrocyte differentiation and hypertrophy."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Death Dis (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41419-021-04458-1"}], "href": "https://doi.org/10.1038/s41419-021-04458-1"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "34930890"}], "href": "https://pubmed.ncbi.nlm.nih.gov/34930890"}]}]}]}