{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nSTAMBP (also known as AMSH) is a JAMM‐family deubiquitinating enzyme that plays a central role in endocytic trafficking and receptor fate determination. It cleaves Lys63‐linked polyubiquitin chains from a range of transmembrane proteins—including the epidermal growth factor receptor, PAR2, CXCR4, gap junction protein Cx43, and the calcium‐sensing receptor—to dictate whether internalized cargo is recycled or delivered to lysosomal degradation. STAMBP executes its function by associating with key components of the endosomal sorting complexes required for transport (ESCRT), such as CHMP3 and clathrin, and by interacting with the SH3 domain–containing adaptor protein STAM. Structural and biochemical studies have elucidated how STAMBP is precisely positioned for catalysis by engaging both distal and proximal ubiquitin moieties, thereby ensuring efficient and linkage‐specific deubiquitination."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "16"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nDefective STAMBP function—often due to recessive mutations affecting its stability or substrate interactions—is linked to neurodevelopmental and inflammatory disorders. Patients with microcephaly‐capillary malformation (MIC‐CAP) syndrome exhibit reduced STAMBP expression, the accumulation of ubiquitin–conjugated protein aggregates, and dysregulated intracellular signaling (including perturbations in the RAS–MAPK and PI3K–AKT–mTOR pathways), which contribute to severe microcephaly, intractable seizures, and developmental delay. Moreover, by deubiquitinating inflammasome components such as NALP7 and NLRP3, STAMBP helps to temper IL‑1β–driven inflammatory responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "17", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nElevated expression and enhanced activity of STAMBP have also been implicated in oncogenesis. In several cancers—including esophageal squamous cell carcinoma, lung adenocarcinoma, triple‐negative breast cancer, and pancreatic cancer—overabundant STAMBP contributes to tumor progression by stabilizing oncogenic receptors (such as EGFR), promoting sustained MAPK pathway activation, and fostering cell migration, invasion, and chemoresistance. 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