Tmprss5, also known as spinesin, is a transmembrane serine protease. It has a simple type II transmembrane structure and consists of a cytoplasmic domain, a transmembrane domain, a stem region with a scavenger receptor-like domain, and a serine protease domain [2]. Tmprss5 is predominantly expressed in the central nervous system, especially in neurons, axons, synapses of motoneurons in the spinal cord, and some oligodendrocytes [2]. It may play important roles at the synapses and in oligodendrocytes, and its gene expression in astrocytes is regulated by cAMP [2,3].

In terms of disease associations, genetically predicted plasma levels of Tmprss5 are associated with stroke [1,6]. Body mass index, white matter hyperintensity, and atrial fibrillation appear to mediate the Tmprss5-stroke association [1]. In Charcot-Marie-Tooth disease type 1A (CMT1A), Tmprss5 protein is elevated 2.07-fold in plasma relative to controls and is most highly expressed in Schwann cells of peripheral nerve, which may provide a disease marker for CMT1A [4]. Tmprss5 may also play a role in hearing as potential pathogenic mutations in its gene showed reduced or absent proteolytic activity, and its protein was detected in spiral ganglion neurons and at the plasma membrane [5].

In conclusion, Tmprss5 is a transmembrane serine protease with important functions in the central nervous system. Its involvement in stroke, CMT1A, and potentially hearing loss, as revealed through genetic and biomarker studies, indicates its significance in these disease areas. Further research on Tmprss5 could potentially lead to a better understanding of the underlying disease mechanisms and the development of new therapeutic strategies [1,4,5,6].