CDK5RAP3 and Down syndrome: 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).