KLK1 (kallikrein 1) is a serine-type endopeptidase located on chromosome 19 that functions as a key component of the kallikrein-kinin system 1. Primary roles include regulation of systemic arterial blood pressure, zymogen activation, and microbial defense through cleavage of Neisseria meningitidis NHBA in saliva 1. KLK1 maintains intestinal mucosal barrier integrity by suppressing bradykinin receptor B1-mediated fibroblast phenotypic transition, with reduced expression observed in inflammatory bowel disease and colorectal cancer 2. The gene has emerged as a candidate risk locus for idiopathic pulmonary arterial hypertension (IPAH), identified through genome-wide exome sequencing with variants accounting for approximately 0.4% of PAH Biobank cases; KLK1 variant carriers show later disease onset and moderate phenotypes compared to BMPR2 carriers 3. However, KLK1 was classified as having only limited evidence for PAH causality in clinical genetics guidelines 4. Additionally, KLK1 is implicated in acute kidney injury-to-chr19 kidney disease progression and appears altered in autism spectrum disorder, where it contributes to neuroinflammation 56. Recombinant KLK1 (DM199) shows therapeutic promise in stroke treatment with fewer side effects than conventional tPA 7. KLK1 also participates in asthma pathogenesis and viral respiratory infections 8.