Abstract: The study by Reichard et al. (2025), entitled “DNMT1-mediated regulation of somatostatinpositive interneuron migration impacts cortical architecture and function”, significantly advances our understanding of DNA methyltransferase 1 (DNMT1) in neural development by revealing a critical role in postmitotic SST-expressing cortical interneurons. Using conditional mouse genetics (Sst-Cre/tdTom/Dnmt1 loxP2 mice), live imaging, and functional assays, the authors demonstrate that DNMT1 regulates the expression of key transcription factors required for interneuron subtype identity and migration, such as Arx, in a DNA methylation-dependent manner at the postmitotic level. Loss of DNMT1 disrupts the directed migration of SST+ interneurons, causing premature cortical plate invasion. Notably, these alterations affect the surrounding microenvironment in a non-cell-autonomous fashion, impacting cortical progenitor proliferation and laminar organization. These alterations culminate in impaired cortical function and behavioral deficits related to neurological and neuropsychiatric diseases. Of note, the adult cortex of conditional mutants contained an increased fraction of SST+ interneurons coexpressing parvalbumin, suggesting a fate shift within this lineage. These findings not only highlight a previously underappreciated epigenetic safeguarding of interneuron trajectory and timing at the postmitotic level by DNMT1 but also open new avenues to explore how epigenetic regulators coordinate cellular interactions during corticogenesis—insights with potential relevance for neurodevelopmental disorders involving interneuron dysfunction.