TMPRSS7 (transmembrane serine protease 7), also known as matriptase-3, is a type II transmembrane serine protease that preferentially cleaves peptides with arginine at the P1 position 1. The protein functions as an inactive zymogen that undergoes proteolytic activation through shedding of its catalytic domain into the extracellular space 1. TMPRSS7 plays a critical role in neurodevelopment. Loss-of-function variants in TMPRSS7 cause neurodevelopmental disorder characterized by impaired zymogen synthesis and defective protease shedding 1. Tmprss7 knockout mice exhibit dysregulated synaptic dendritic spine density and function in the cerebral cortex and hippocampus, with associated neurobehavioral deficits including spatial learning impairment, anxiety-like behavior, and reduced social novelty preference 1. These effects involve disrupted synaptic signaling pathways 1. Beyond neurodevelopment, TMPRSS7 variants associate with disease susceptibility. Specific TMPRSS7 SNPs (rs1844925 and rs2399403) correlate with breast cancer risk and prognosis, with combined variants increasing mortality risk 2. A TMPRSS7 variant (rs147783135) also associates with reduced ischemic stroke risk 3. Additionally, TMPRSS7 is expressed in oral tissues including salivary glands and epithelial cells, suggesting potential roles in oral pathophysiology 4.