Physiological roles of TMEM63 protein family
| Member . | Expression . | Related physiology/pathology . | Ref . |
|---|---|---|---|
| TMEM63A | Oligodendrocytes and central nervous system | Mutations cause infantile hypomyelinating leukodystrophy | Yan et al. (2019) |
| Mutation identified in infantile hypomyelinating leukodystrophy | Tonduti et al. (2021) | ||
| Mutations cause infantile hypomyelinating leukodystrophy with global developmental delay | Fukumura et al. (2022) | ||
| Modulates myelin and myelin-associated protein production | Halford et al. (2025) | ||
| Triple-negative breast cancer | Acts as an oncogene; involved in autophagy-mediated degradation pathway | Zhang et al. (2023b) | |
| Diffuse large B cell lymphoma | Potential therapeutic target; knockout inhibits diffuse large B cell lymphoma proliferation | Wu et al. (2022) | |
| Dorsal root ganglion neurons | Mediates macrophage infiltration and pro-inflammatory cytokine release, leading to pain hypersensitivity in chronic postamputation pain | Pu et al. (2023) | |
| Alveolar type 2 epithelial cells, lung | Mediates lung inflation-induced surfactant and ATP release | Chen et al. (2024) | |
| TMEM63B | Alveolar type 2 epithelial cells, lung | Mediates lung inflation-induced surfactant and ATP release | Chen et al. (2024) |
| Intestinal stem cells and small intestine | Regulates intestinal stem cell proliferation and motility | Tu et al. (2024) | |
| Subfornical organ neurons | Directly responds to hyperosmolarity in thirst | Zou et al. (2025) | |
| Osmosensor detecting systemic hyperosmolality for thirst drive | Yang et al. (2024) | ||
| Cochlear sensory epithelial cells, inner ear | Regulates the regression of the greater epithelial ridge for normal onset of hearing | Ye et al. (2024) | |
| Outer hair cells and inner ear | Osmosensing regulates cell volume | Du et al. (2020) | |
| Brain | Gain-of-function variants cause neurodevelopmental disorder with epilepsy and neurodegeneration | Vetro et al. (2023) | |
| Pancreatic β-cells | Responds to glucose-induced swelling, triggering depolarization and insulin secretion | Tu et al. (2025) | |
| Olfactory interneurons | Mediates mechanical signaling for somal translocation during neuronal migration | Minegishi et al. (2025) | |
| TMEM63C | Podocytes and kidney | Downregulated in angiotensin II-induced podocyte apoptosis | Eisenreich et al. (2020) |
| Downregulation causes podocyte loss; restoring TMEM63C rescues their viability | Orphal et al. (2020) | ||
| Essential for normal kidney filtration barrier function | Schulz et al. (2019) | ||
| Nervous system | Dysfunction disrupts ER-mitochondrial contact sites in hereditary spastic paraplegia | Tábara et al. (2022) |
| Member . | Expression . | Related physiology/pathology . | Ref . |
|---|---|---|---|
| TMEM63A | Oligodendrocytes and central nervous system | Mutations cause infantile hypomyelinating leukodystrophy | Yan et al. (2019) |
| Mutation identified in infantile hypomyelinating leukodystrophy | Tonduti et al. (2021) | ||
| Mutations cause infantile hypomyelinating leukodystrophy with global developmental delay | Fukumura et al. (2022) | ||
| Modulates myelin and myelin-associated protein production | Halford et al. (2025) | ||
| Triple-negative breast cancer | Acts as an oncogene; involved in autophagy-mediated degradation pathway | Zhang et al. (2023b) | |
| Diffuse large B cell lymphoma | Potential therapeutic target; knockout inhibits diffuse large B cell lymphoma proliferation | Wu et al. (2022) | |
| Dorsal root ganglion neurons | Mediates macrophage infiltration and pro-inflammatory cytokine release, leading to pain hypersensitivity in chronic postamputation pain | Pu et al. (2023) | |
| Alveolar type 2 epithelial cells, lung | Mediates lung inflation-induced surfactant and ATP release | Chen et al. (2024) | |
| TMEM63B | Alveolar type 2 epithelial cells, lung | Mediates lung inflation-induced surfactant and ATP release | Chen et al. (2024) |
| Intestinal stem cells and small intestine | Regulates intestinal stem cell proliferation and motility | Tu et al. (2024) | |
| Subfornical organ neurons | Directly responds to hyperosmolarity in thirst | Zou et al. (2025) | |
| Osmosensor detecting systemic hyperosmolality for thirst drive | Yang et al. (2024) | ||
| Cochlear sensory epithelial cells, inner ear | Regulates the regression of the greater epithelial ridge for normal onset of hearing | Ye et al. (2024) | |
| Outer hair cells and inner ear | Osmosensing regulates cell volume | Du et al. (2020) | |
| Brain | Gain-of-function variants cause neurodevelopmental disorder with epilepsy and neurodegeneration | Vetro et al. (2023) | |
| Pancreatic β-cells | Responds to glucose-induced swelling, triggering depolarization and insulin secretion | Tu et al. (2025) | |
| Olfactory interneurons | Mediates mechanical signaling for somal translocation during neuronal migration | Minegishi et al. (2025) | |
| TMEM63C | Podocytes and kidney | Downregulated in angiotensin II-induced podocyte apoptosis | Eisenreich et al. (2020) |
| Downregulation causes podocyte loss; restoring TMEM63C rescues their viability | Orphal et al. (2020) | ||
| Essential for normal kidney filtration barrier function | Schulz et al. (2019) | ||
| Nervous system | Dysfunction disrupts ER-mitochondrial contact sites in hereditary spastic paraplegia | Tábara et al. (2022) |
Summary of all established physiological and pathological functions of TMEM63s, including mechanosensation and osmoregulation processes in specific cell types.