MYSM1, a metalloprotease family protein, has deubiquitinase catalytic activity along with SANT and SWIRM domains. It is a crucial regulator in multiple biological processes. In the nucleus, it interacts with chromatin to regulate gene expression via histone H2A deubiquitination and non-catalytic contacts with other transcriptional regulators. In the cytosol, it regulates innate immunity signal transduction pathways by promoting deubiquitination of TRAF3, TRAF6, and RIP2 [1].

MYSM1 knockout mice show developmental abnormalities across multiple tissues and organs. In neural stem cells (NSCs), Mysm1 knockdown in mice led to abnormal brain development with microcephaly. Mysm1 deletion promoted NSC proliferation and apoptosis, skewing differentiation towards neurogenesis [5]. In the hematopoietic system, MYSM1 deficiency in humans causes a rare hereditary disorder with leukopenia, anemia, and other hematopoietic and developmental abnormalities. In hematopoietic stem cells (HSCs), reduced MYSM1-related protein synthesis increases ferroptosis [1,4]. In triple-negative breast cancer (TNBC), overexpressing MYSM1 increased cisplatin-induced apoptosis [2]. In doxorubicin-induced cardiotoxicity, genetic knockdown of MYSM1 mitigated cardiomyopathy [3].

In conclusion, MYSM1 is essential for tissue development and function, regulating processes such as stem cell proliferation and differentiation, immune responses, and apoptosis. MYSM1-deficient mouse models have revealed its role in diseases like hematopoietic disorders, TNBC, and cardiotoxicity, providing valuable insights into disease etiology and potential therapeutic targets.