TMPRSS5 (transmembrane serine protease 5) is a serine-type peptidase localized to the plasma membrane that may play important roles in hearing and peripheral nerve function. In the inner ear, TMPRSS5 is expressed in spiral ganglion neurons and has been implicated in auditory function through genetic studies; mutations in TMPRSS5 show reduced or absent proteolytic activity and are associated with nonsyndromic hearing loss 1. Beyond auditory function, TMPRSS5 serves as a novel Schwann cell-specific biomarker. The protein is most highly expressed in Schwann cells of peripheral nerve and is elevated 2.07-fold in plasma of Charcot-Marie-Tooth disease type 1A (CMT1A) patients compared to controls, demonstrating early myelination deficits specific to this form of peripheral neuropathy 2. TMPRSS5 elevation correlates with Schwann cell-associated microRNAs in CMT1A and provides disease specificity not observed in other CMT subtypes 3. The protein also serves as a candidate biomarker for CMT1A in clinical trials 4. Genetically, TMPRSS5 shows causal associations with ischemic stroke risk across diverse populations, with genetically predicted elevated plasma levels associated with increased stroke risk 56. Additionally, common variants in TMPRSS5 are associated with age-related nuclear cataract, suggesting roles in maintaining lens integrity 7. TMPRSS5 represents a potentially novel therapeutic target for stroke and peripheral neuropathies.