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Transmembrane protein 64 (TMEM64)
- Target
- TMEM64
- Molecular classification
- Transmembrane protein, Regulator of signaling pathways (specifically Ca²⁺ signaling), Other (not a GPCR, ion channel, enzyme, transporter, or receptor per current evidence)
01
Overview
Transmembrane protein 64 (TMEM64) is a membrane protein localized to the endoplasmic reticulum, involved in regulating cellular calcium signaling and differentiation. It interacts with SERCA2 to enhance TNFSF11 (RANKL)-dependent pathways, critical for osteoclast activation and mitochondrial ROS generation, facilitating bone remodeling. TMEM64 suppresses osteoblast differentiation while promoting adipogenesis through inhibition of the Wnt signaling pathway, mediating mesenchymal stem cell lineage selection. TMEM64 is overexpressed in some cancers (notably hepatocellular carcinoma), suggesting a role in disease, but it is not currently the target of approved drugs. This molecule is considered a therapeutic target due to its roles in bone metabolism and cancer.
- Other names
- TMEM64TMM64_HUMANTransmembrane protein TMEM64
02
Biological functions
Positive regulator of osteoclast differentiation (bone-resorbing cell development)Regulation of TNFSF11 (RANKL)-induced Ca²⁺ signaling via SERCA2 interactionNegative regulation of osteoblast differentiationPositive regulation of adipocyte differentiationModulation of canonical Wnt signaling pathwayRegulation of cell lineage commitment in mesenchymal stem cells
03
Disease associations
Bone disease (osteoclast/osteoblast balance, possible role in osteoporosis)Cancer (highly expressed in hepatocellular carcinoma and promotes tumor cell proliferation)Other (rare viral hemorrhagic fevers reported in genetic association, e.g., Alkhumra and Kyasanur Forest Disease, but mechanistic links are unclear)
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