Ptpn11, encoding tyrosine phosphatase SHP-2, is located on chromosome 12 (12q24.1) and expresses in most embryonic and adult tissues. It plays crucial roles in cell proliferation, differentiation, survival and death, participating in signaling events downstream of RAS-MAPK and JAK/STAT pathways [1].

Germline mutations in Ptpn11 cause Noonan syndrome (NS) and LEOPARD syndrome (LS), while somatic mutations contribute to leukemogenesis. In NS-affected patients, Ptpn11 is one of the genes with a significant number of pathogenic variants. Exons 3, 8 and 13 had the highest number of pathogenic variants in a study of 107 NS-affected individuals. Congenital cardiac anomalies were present in 84% of the mutation-positive cohort, mostly on the right side of the heart. Other common features included short stature, pectus excavatum, and cryptorchidism in males [2,3,6]. In addition, NS and NS with Multiple Lentigines (NSML) related to Ptpn11 mutations both contain phenotypes like deafness, craniofacial anomalies, skin disorders, ophthalmologic abnormalities and cancer predisposition [1]. Ptpn11 mutations are also found in a subset of human and canine visceral disseminated histiocytic sarcoma [7]. Aberrant SHP2 (product of Ptpn11) expression or activation has implications in the development, progression and metastasis of many solid tumors, and it is involved in multiple signaling cascades such as RAS-RAF-MEK-ERK, PI3K-AKT, JAK-STAT and PD-L1/PD-1 pathways. It may have a tumor-promoting or-suppressive role depending on the context [4]. High Ptpn11 expression in diabetic tumor tissues predicts poor prognosis in colorectal cancer, and it is strongly associated with immune infiltrating cells in CRC [5].

In conclusion, Ptpn11 is essential for multiple cellular processes through its involvement in key signaling pathways. Studies on Ptpn11-related mutations in various genetic models, especially in the context of NS, LS, leukemia, and some solid tumors, have provided valuable insights into the gene's role in disease development. These findings help in understanding the underlying molecular mechanisms and may potentially guide the development of targeted therapies for these diseases.