Apart from its importance as a regulator of DDR protein recruitment to DNA breaks [30], the significance of RNF168-dependent functions on human health became apparent following the identification of biallelic mutations in RNF168 as the underlying cause of RIDDLE syndrome, which is clinically characterised by the presence of Radiosensitivity, ImmunoDeficiency, Dysmorphic features, and LEarning difficulties [42,44]. Here, RNF168 is linked to RIDDLE syndrome.