PRSS16 is a serine protease specifically expressed by cortical thymic epithelial cells (cTEC) in the thymus 1. The gene is located on human chromosome 6.3-p22, within the HLA class I region 1. Originally proposed to play a role in T-cell positive selection through peptide antigen processing 2, subsequent studies using Prss16-deficient mice revealed that PRSS16 is not required for quantitatively normal T-cell development, though it may have more subtle regulatory functions 2. PRSS16 expression is developmentally regulated, with embryonic expression coinciding with T-cell precursor colonization of the thymus 1. The gene undergoes alternative splicing to generate at least five transcripts with tissue and age-specific expression patterns, with different isoforms predominating in newborn versus adult thymi 3. Expression levels are altered in autoimmune-prone mice, suggesting a potential role in autoimmunity 1. PRSS16 is also implicated in schizophrenia pathophysiology through a miR-148b-3p/ZNF804A/PRSS16 regulatory pathway in neuronal cells 4. Clinically, PRSS16 polymorphisms have been investigated as candidate susceptibility factors for type 1 diabetes and celiac disease, though direct causative variants remain unidentified 5. PRSS16 expression patterns serve as a differentiation marker for cortical thymic epithelial cells in thymoma classification 6, and PRSS16 is included in a degradome-derived gene signature predicting metastasis risk in cervical cancer 7.