SHP-2, also known as PTPN11, is a non-receptor protein tyrosine phosphatase containing two Src homology 2 (SH2) domains and a phosphatase domain. Phosphorylation at Tyr542 and another site, Tyr580, in the C-terminal tail are crucial for SHP-2 activation and function as binding sites for proteins with SH2 domains, such as GRb2. SHP-2 is a key regulator in multiple signaling pathways, including the Ras-Raf-MEK-ERK, JAK-STAT, PI3K-AKT-mTOR, and PD-1/PD-L1 pathways. It can act as both an oncogene and a tumor suppressor, depending on the cellular context. SHP-2 plays a role in various cellular processes such as cell growth, differentiation, mitotic cycle, and oncogenic transformation. It is widely expressed in most tissues and is involved in signal transduction from the cell surface to the nucleus. SHP-2 is involved in regulating immune cell functions in the tumor microenvironment and is a target for cancer immunotherapy. It plays a role in the downstream signaling of immune-inhibitory receptors such as PD-1, which is a key target for cancer immunotherapy.