While functionally validated in zebrafish, the role of REL in the 2p15p16.1 syndrome remains unclear because biallelic mutations of REL inherited from healthy parents have recently been identified in patients suffering from a severe form of immunodeficiency, however with no cognitive disability nor brain anomalies (Beaussant − Cohen et al. 2019; Lévy et al. 2021). Here, REL is linked to immune system disorder.