ABRAXAS2 is a scaffolding protein of the BRISC (BRCC3 isopeptidase complex), a K63-specific deubiquitinase complex with diverse cellular functions 12. As a central scaffold, ABRAXAS2 assembles and retains BRISC components in the cytoplasm 2. The complex regulates JAK2 signaling in hematopoietic stem cells through K63-deubiquitination, constraining HSC expansion 3. ABRAXAS2 is essential for mitotic spindle assembly via NUMA1 deubiquitination and kinetochore-microtubule attachment 4. In DNA damage responses, ABRAXAS2 independently promotes USP7-p53 interactions, enhancing p53 deubiquitination and stabilization to drive apoptosis 5. The protein modulates interferon signaling by deubiquitinating IFNAR1, increasing its stability and cell surface expression 67, and suppresses bacterial lipopolysaccharide responses through this pathway 6. Pathologically, ABRAXAS2 is a target of bacterial T3SS effectors; the EHEC effector NleG6 triggers ABRAXAS2 degradation via selective autophagy, inhibiting NF-κB-mediated inflammation 8. Genetic variants in ABRAXAS2 associate with bone mineral content variation in Hispanic children 9 and with miscarriage risk in polycystic ovary syndrome 10. These findings establish ABRAXAS2 as a multifunctional hub regulating immunity, DNA repair, mitosis, and metabolism.