PTPN11 encodes SHP-2, a protein tyrosine phosphatase that plays critical roles in cellular signaling and development. The protein functions downstream of receptor tyrosine kinases in the RAS-MAPK pathway, positively regulating MAPK signaling through dephosphorylation of various substrates including GAB1, ARHGAP35, and EGFR 1. SHP-2 is essential for multiple developmental processes including heart, brain, and skeletal development, with expression in most embryonic and adult tissues 2. Germline PTPN11 mutations cause Noonan syndrome (NS) in approximately 50% of cases, characterized by congenital heart defects, facial dysmorphisms, short stature, and developmental delays 34. Different mutation classes have distinct effects: NS-associated mutations cause moderate gain-of-function, while leukemia-associated somatic mutations produce stronger activation, and LEOPARD syndrome mutations result in loss-of-function 1. The most common cardiac manifestation in NS patients with PTPN11 mutations is pulmonary stenosis, though atrial septal defects are also frequent 56. PTPN11 variants significantly increase congenital heart disease risk and are also found in histiocytic sarcomas, highlighting the gene's importance in both development and oncogenesis 57.