TMEM63B: a force-sensing channel and scramblase emerges as a drug target
- TMEM63B, a TCS-family protein, works as both a force- and osmolarity-gated ion channel and a lipid scramblase.
- Structures capture separate channel and scramblase states, and patient mutations connect it to epilepsy, hemolytic anemia, and placental, lung and gut defects.
- Drug discovery routes include allosteric gating modulators, isoform- or tissue-selective approaches to limit on-target toxicity, and agonist antibody YN9303-24 for loss-of-function disease.
💡 Points Based on the abstract
Dual-function targets are an assay headache: before trusting any SAR, I'd want to know whether a hit shifts gating, scrambling, or both, so pressure-clamp patch recording plus annexin V scrambling readouts are the minimum. The patient mutations give genuine human genetics, but with expression this broad, an agonist antibody like YN9303-24 only makes sense if tissue selectivity holds up.