QSOX2 (quiescin sulfhydryl oxidase 2) is a nuclear membrane protein that catalyzes the oxidation of sulfhydryl groups to form disulfide bonds, serving as a critical regulator of protein folding and cellular signaling 1. The enzyme functions as a gatekeeper at the nuclear membrane, controlling the stabilization and nuclear import of phosphorylated STAT5B, thereby regulating growth hormone signaling pathways essential for normal growth 1. In cancer contexts, QSOX2 promotes tumor stemness and chemoresistance by enhancing disulfide bond formation in TSC2, which stabilizes TSC2-Akt interactions and activates the mTOR/c-Myc signaling axis 2. QSOX2 is highly expressed in esophageal squamous cell carcinoma and associated with poor prognosis 2. The protein has been identified as a novel polysialylated protein secreted from breast cancer cells 3. Genetic variants in QSOX2 cause a rare syndrome characterized by short stature, immune dysfunction, gastrointestinal dysmotility, and mitochondrial abnormalities, demonstrating its essential role in multiple physiological processes 1. Additionally, QSOX2 has emerged as a potential therapeutic target, with genetic evidence suggesting protective effects against atrial fibrillation 4.