TRIM72 (also called MG53) is a muscle-specific E3 ubiquitin ligase with dual roles in membrane repair and metabolic regulation. Primary function: TRIM72 nucleates assembly of repair machinery at sites of cell membrane damage through a redox-sensing mechanism 1. Upon membrane injury, the oxidative environment triggers disulfide bond formation and homooligomerization of TRIM72, which recruits TRIM72-containing vesicles to form membrane patches and facilitates transport of DYSF to injury sites 1. The protein interacts with phosphatidylserine-enriched membranes, essential for its oligomeric assembly and ubiquitination activity 1. Beyond membrane repair, TRIM72 functions as an E3 ubiquitin ligase with broader cellular impacts. It ubiquitinates multiple substrates: SRSF5 (regulating PKM2 expression and cancer metabolism) 2, AMPKα (suppressing AMPK signaling under high glucose) 3, ATF2 (reducing TLR4 expression in sepsis) 4, and ADAM9 (regulating ferroptosis in preeclampsia) 5. Clinical significance: TRIM72 mediates cardioprotection during ischemic preconditioning through H₂O₂-triggered secretion 6. Anti-TRIM72 autoantibodies emerge as diagnostic markers in idiopathic inflammatory myopathies 7. TRIM72 exhibits anti-tumor effects in colorectal cancer, liver cancer, and small cell lung cancer 8, though its E3 ligase activity paradoxically contributes to insulin resistance and metabolic dysfunction 8.