Mbd1, or methyl-CpG-binding domain protein 1, is highly associated with DNA methylation, an important epigenetic regulation mechanism in normal development and cancer [1,3,6]. Its MBD domain binds to methylated CpGs, triggering H3K9 methylation and transcriptional repression, while the CXXC3 domain allows it to bind to unmethylated DNA, making it a unique member of the MBD family [1,3]. Mbd1 functions as an epigenetic regulator through mechanisms like forming the MCAF1/MBD1/SETDB1 or MBD1-HDAC3 complexes [1].

In various disease-related studies, Mbd1 has been shown to play diverse roles. In gastric cancer, the MBD1/HDAC3 complex transcriptionally inhibits miR-5701, which targets the oncogene FGFR2, promoting cancer development [2]. In pancreatic cancer, Mbd1 silencing decreases antioxidant response through epigenetic regulation of KEAP1, indicating its role in the antioxidant response pathway [4]. In gallbladder cancer, Mbd1 is upregulated, promoting malignant behaviors and chemotherapeutic resistance to gemcitabine, suggesting it as a potential therapeutic target [5]. In the context of pain, DRG Mbd1-deficient mice show reduced acute and neuropathic pain responses, as Mbd1 represses Oprm1 and Kcna2 gene expression by recruiting DNMT3a [7].

In conclusion, Mbd1 is a crucial epigenetic regulator involved in DNA methylation-related transcriptional regulation. Studies using gene-knockout models, such as the DRG Mbd1-deficient mice, have revealed its significant roles in multiple disease conditions including cancer and pain-related disorders, highlighting its potential as a therapeutic target in these areas.