DEAF1 is a multifunctional transcription factor that regulates gene expression through binding to unmethylated CpG-containing DNA sequences 1. Primary functions include transcriptional repression of specific genes via sequence-specific binding to motifs like 5'-TTC[CG]G-3' 1, and activation of genes including EIF4G3 and the 5-HT1A receptor through both direct and indirect mechanisms 2. Mechanistically, DEAF1 acts downstream of FOXO signaling to regulate muscle regeneration and aging by suppressing autophagy genes PIK3C3 and ATG16L1 34. Exercise-induced FOXO activation suppresses DEAF1 expression, normalizing mTORC1 activity and reversing muscle aging 4. DEAF1 phosphorylation by GSK3β regulates 5-HT1A repression, with lithium inhibiting this pathway 2. Disease relevance spans neurodevelopmental and muscular domains. De novo variants cause DEAF1-associated neurodevelopmental disorder (DAND) with intellectual disability, speech delay, autism, and sleep disturbances through dominant-negative mechanisms, while biallelic variants additionally cause microcephaly with partial loss of function 56. DEAF1 promotes hepatocellular carcinoma progression by enhancing glutamine transporter expression and reducing oxidative stress 7. Clinically, detailed phenotypic analysis and functional studies are essential for variant pathogenicity determination in DAND patients 5, while FOXO-DEAF1-mTORC1 axis modulation offers therapeutic potential for sarcopenia and age-related muscle loss 4.