Transmembrane protein 63B (TMEM63B)

Transmembrane protein 63B (TMEM63B) is a membrane-bound protein that serves dual roles as a mechanosensitive cation channel and a lipid scramblase. It regulates bidirectional movement of phospholipids, especially phosphatidylcholine and sphingomyelin, in response to changes in membrane curvature and thickness, helping maintain plasma membrane lipid asymmetry. TMEM63B supports calcium influx in response to osmotic stress, influences neuronal signaling related to thirst, enables surfactant secretion for respiration in alveolar cells, and is crucial for maintaining cochlear outer hair cell morphology and hearing. Genetic mutations can confer constitutive scramblase activity, disrupting normal membrane lipid distribution, and are implicated in rare epilepsies, neurodevelopmental disorders, and spastic paraplegia. TMEM63B does not currently have direct approved pharmaceutical modulators, but its functional profile makes it of therapeutic interest, particularly in diseases related to membrane structure or mechanosensation.

Other names

C6orf110 (previous symbol)TM63B (UniProtKB: Q5T3F8)GC06P044203 (GeneCards ID)A0A8J1JLL3 (InterPro)D4A105 (InterPro)

For lipid scramblase function: drugs would hypothetically modulate lipid scrambling activity, affecting phospholipid asymmetry and membrane signaling. For ion channel function: drugs could alter mechanosensitivity or calcium flux across the plasma membrane. No current drugs described; mechanisms inferred from protein activity.