A recent study (Hamagami et al., 2023) investigating Nsd1 function revealed that NSD1 defines where non-CG methylation can and cannot be deposited, and that alterations in DNA methylation and gene expression resultant from Nsd1 disruption overlap with those seen in a mouse model of TBRS (Fig. 2). The gene discussed is NSD1; the disease is Tatton-Brown-Rahman overgrowth syndrome.