Smg1, also known as kinase suppressor of morphogenesis in genitalia 1, is a key regulator in the nonsense-mediated mRNA decay (NMD) pathway. NMD is essential for mammalian embryonic development, brain development, and modulation of the stress response. As a member of the phosphatidylinositol 3-kinase-related kinase family, Smg1 phosphorylates UPF1, a key NMD factor, to initiate the decay of premature stop codon-containing mRNAs [2,5].

In multiple myeloma, CC-115, which inhibits Smg1, shows superior antitumor activity over TORK inhibitors in primary human MM cells and xenograft mouse models, suggesting Smg1 as a candidate therapeutic target [1]. In Atm null mice, Smg1 heterozygosity exacerbates haematopoietic cancer development by increasing persistent DNA damage and oxidative stress [3]. Also, in acute myeloid leukemia, SMG1 acts as a potential tumor suppressor with epigenetic regulation as its promoter hypermethylation down-regulates its expression, and demethylating agents restore its expression and inhibit cell growth [4].

In conclusion, Smg1 plays a crucial role in the NMD pathway, with implications in multiple biological processes and disease conditions. Studies using gene knockout or conditional knockout mouse models have revealed its role in cancer development, highlighting its potential as a therapeutic target in cancers such as multiple myeloma and acute myeloid leukemia.