STAM2 (signal transducing adaptor molecule 2) functions as a critical adaptor protein in intracellular signaling and endosomal trafficking pathways. The protein plays essential roles in cytokine-mediated signal transduction, particularly in IL-2 and GM-CSF signaling pathways that lead to DNA synthesis and MYC induction through association with JAK2 and JAK3 kinases 1. As a component of the ESCRT-0 complex, STAM2 collaborates with HRS to regulate ubiquitin-dependent receptor trafficking and multivesicular body formation, containing three ubiquitin-binding domains (VHS, UIM, and SH3) that recognize ubiquitinated cargo proteins 23. In cancer contexts, STAM2 demonstrates oncogenic properties through multiple mechanisms: it promotes bladder cancer metastasis when stabilized by O-GlcNAcylation, which enhances JAK2/STAT3 signaling and epithelial-mesenchymal transition 4; it facilitates gastric cancer progression via JAK2/STAT3 pathway activation 5; and it specifically regulates PD-L1 secretion via small extracellular vesicles in oral squamous cell carcinoma by directly binding PD-L1 and recruiting HRS 6. Additionally, STAM2 participates in cellular stress responses, where its interaction with HSPA1A modulates autophagy and thermal resistance 7. The protein shows high expression in gastrointestinal stromal tumors, correlating with proliferative markers 8.