ADAMTS19 is a metalloproteinase that plays critical roles in cardiac valve development and extracellular matrix organization. Functionally, ADAMTS19 is expressed in valvular interstitial cells and positioned within the Wnt-ADAMTS19-Klf2 regulatory axis, which is essential for proper valve maturation and maintenance 1. Loss of ADAMTS19 function impairs this balance, leading to progressive heart valve disease affecting multiple valves early in life 1. Mechanistically, ADAMTS19 regulates extracellular matrix proteolysis and collagen fibril organization, processes fundamental to valve structure and function 2. Beyond cardiac development, ADAMTS19 modulates alpha-synuclein phase separation relevant to Parkinson's disease pathogenesis 3. Clinically, ADAMTS19 mutations cause cardiac valvular dysplasia 2, a monogenic form of progressive valve disease 1. Additionally, ADAMTS19 has been implicated in ovarian function, with genetic interactions between ADAMTS19 and ACVR2B polymorphisms associated with premature ovarian failure susceptibility 4. Recent genomic studies identify ADAMTS19 among key genes contributing to aortic valve disease development, including bicuspid aortic valve phenotypes 5, positioning it as an emerging therapeutic target for valve disorders.