CRISPR/Cas9–modified mice, in which CS-associated single nucleotide mutations have been introduced into native KCNJ8 (Kir6.1[V65M]) or ABCC9 (SUR2[A478V]) loci provide tractable animal models in which to understand cellular mechanisms and organ consequences of CS (Huang et al., 2018), and this has led to the recognition of the role of channel overactivity in vascular smooth muscle in generating the cardiovascular phenotype CS (McClenaghan et al., 2020). The gene discussed is KCNJ8; the disease is Cowden syndrome 1.