TMEM266 is a voltage-sensor protein localized to the post-synaptic side of glutamatergic mossy fibers and granule cells in the cerebellum 12. Despite containing an S1-S4 voltage-sensing domain characteristic of ion channels, TMEM266 does not form a functional ion channel and instead functions as a non-canonical voltage sensor 2. The protein exhibits functional voltage sensitivity, undergoing both rapid (microsecond) and slow (millisecond) structural rearrangements in response to membrane voltage changes 2. A zinc-binding site in TMEM266 regulates the slow conformational transition, suggesting extracellular zinc modulates its voltage-sensing properties 2. TMEM266 forms oligomeric complexes and is enriched in cerebellar granule cell layer differentiation from human induced pluripotent stem cells 3. Epigenetically, TMEM266 shows altered DNA methylation patterns associated with neonatal morbidities in very preterm infants, potentially linking the gene to neuronal development and signaling 4. The precise physiological role of TMEM266's voltage-sensing capability remains unclear, though its rapid voltage responsiveness may have utility as a genetically encoded voltage indicator 2.