MYSM1 is a metalloprotease deubiquitinase with critical roles spanning hematopoiesis, immune regulation, and tissue homeostasis 1. In the nucleus, MYSM1 acts as a transcriptional coactivator by removing monoubiquitin from histone H2A, enabling derepression of genes essential for stem cell differentiation and blood cell development 1. Cytoplasmic MYSM1 suppresses innate immunity by catalyzing K63-linked deubiquitination of signaling proteins including TRAF3, TRAF6, and RIPK2, thereby attenuating inflammatory responses 1. Mutations in MYSM1 cause bone marrow failure syndrome 4, characterized by pancytopenia and developmental abnormalities, reflecting its essential role in hematopoietic stem cell maintenance 2. Studies reveal MYSM1 deficiency increases ferroptosis vulnerability in hematopoietic stem cells, which can be rescued by ferroptosis inhibition 3. Conversely, elevated MYSM1 expression promotes cardiotoxicity through ferroptosis enhancement 4 and myocardial ischemia/reperfusion injury via STAT1 stabilization 5. In cancer, MYSM1 acts as a tumor suppressor in colorectal cancer by epigenetically activating miR-200/CDH1 expression and inhibiting PI3K/AKT signaling 6, while its upregulation promotes melanoma cell growth 7. These context-dependent functions underscore MYSM1's dual roles as a critical regulator in normal physiology and disease pathogenesis 8.