Transmembrane protein 165 (TMEM165)

TMEM165 encodes a seven-pass transmembrane protein localized mainly to the Golgi apparatus and, in part, lysosomes. It is vital for ion transport (primarily Ca²⁺ and Mn²⁺) and maintenance of proper glycosylation of proteins and lipids through regulation of Golgi ion homeostasis and acidic pH. Loss-of-function mutations cause congenital disorders of glycosylation with multisystemic symptoms, and TMEM165 is also involved in lysosomal calcium handling important for cellular survival under stress. In cancer, TMEM165 is overexpressed in aggressive tumor types (e.g., HCC, breast carcinoma), promoting invasive capacity via upregulation of MMP-2, and is emerging as both a biomarker and a putative therapeutic target for limiting cancer progression. Currently, there are no approved drugs that directly target TMEM165, but its function can be modulated indirectly by altering ion availability (e.g., manganese supplementation). Defective TMEM165 impacts both glycosylation and cell signaling pathways, underscoring its significance in cell biology and pathology.

Other names

Putative divalent cation/proton antiporter TMEM165TPARLTMPT27GDT1SLC64A1Transmembrane protein PT27Transmembrane protein TPARLTPA regulated locusCDG2KFT27

Antiport of Ca²⁺/Mn²⁺ for H⁺ across Golgi or lysosomal membranes. Regulates luminal Golgi and lysosomal pH and cofactor supply for glycosyltransferases. Influences matrix metalloproteinase (MMP-2) expression affecting metastasis.