Recent Advances in Research on SHP Family Phosphatases: Signal Regulation Mechanisms and Disease Associations.

The protein tyrosine phosphatase family comprises a large number of members. Among them, Src homology 2 (SH2) domain-containing protein tyrosine phosphatases (commonly referred to as the SHP family). Members of the SHP family regulate multiple signaling pathways by catalyzing the dephosphorylation of substrate proteins, thereby participating in fundamental biological processes such as immune regulation and cell proliferation. Their normal function is essential for maintaining organismal homeostasis. Extensive evidence indicates that dysregulation of SHP family members is closely associated with a variety of diseases. Accordingly, this review summarizes the functional characteristics of SHP-1 and SHP-2, with particular emphasis on advances in their structural regulation, substrate recognition, signaling pathway regulation, and disease-related mechanisms. It further discusses key controversies and unresolved scientific questions concerning SHP family regulation, as well as recent advances in targeted therapeutic strategies, thereby contributing to a deeper understanding of SHP family biology and informing the development of precision therapies.