Rho GTPase-activating protein 21 (ARHGAP21) (MIM: 609870) encodes a member of the RhoGAP family that is predominantly expressed in the brain (https://www.proteinatlas.org/). The ARHGAP21 protein localizes to the Golgi apparatus via interaction with ADP-ribosylation factor 1 (ARF1) protein, where it inhibits cell division cycle 42 (CDC42) activity to regulate the actin-related protein complex 2/3 (ARP2/3) complex and actin dynamics. These processes are essential for maintaining Golgi structure and cytoskeletal organization, which are crucial for cell–cell junctions and adhesion.1 Previous studies have shown that variants in ARHGAP21, ARF1, and CDC42 are associated with neurodevelopmental disorders (NDDs) and seizures/epilepsies (https://www.hgmd.cf.ac.uk/). While ARF1 (MIM: 103180) and CDC42 (MIM: 116952) are established causative genes, the pathogenic relevance of ARHGAP21 variants in epilepsy/NDDs remains to be elucidated.