Tmprss2, also known as transmembrane serine protease 2, is a type II transmembrane protease. It is widely expressed in epithelial cells of multiple organs like the respiratory and gastrointestinal tract, and the prostate [3]. Tmprss2 is synthesized as a zymogen and undergoes autolytic activation. It has a crucial function in priming viral spike proteins, facilitating viral entry into host cells, which is essential for viral infectivity. It is also involved in the entry processes of several respiratory viruses, such as SARS-CoV-2 [3,4,5,6,7].

Four endemic seasonal human coronaviruses circulate worldwide, and Tmprss2 is a functional receptor for human coronavirus HKU1. It triggers HKU1 spike-mediated cell-cell fusion and pseudovirus infection. Catalytically inactive Tmprss2 mutants allow pseudovirus infection despite not cleaving the HKU1 spike. Tmprss2 binds with high affinity to the HKU1 receptor binding domain but not to SARS-CoV-2 [1]. Additionally, in lung cancer, PM2.5 can activate AhR to upregulate Tmprss2 and IL18 expression, promoting cancer progression, and depletion of Tmprss2 in lung cancer cells suppresses tumor-related growth [2].

In conclusion, Tmprss2 is of great biological importance for its role in viral entry and in some disease processes. Studies related to Tmprss2 in the context of HKU1 infection and lung cancer progression have provided insights into its functions. Understanding Tmprss2 could potentially offer new strategies for combating viral infections and treating related diseases.