Interestingly, UFM1, UFL1, and CDK5RAP3 are all key components of the UFMylation pathway which is an ubiquitin-like posttranslational protein modification (20, 21), while TTC3 is an E3 ubiquitin ligase highly expressed in the CNS and is closely involved in Down syndrome (24, 25). Here, TTC3 is linked to Down syndrome.