UFL1

UFL1 (UFM1-specific ligase 1), also known as KIAA0776 or RCAD, is a core E3 ligase in the UFMylation pathway. It mediates the final step of UFM1 conjugation to substrates (e.g., CDK5RAP3) by interacting with UBA5 (E1) and UFC1 (E2), regulating protein stability and cellular processes like ER stress response and cell proliferation.
Dysfunctionl UFL1 is associated with neurodevelopmental disorders (e.g., intellectual disability) due to impaired neuronal UFMylation, and liver injury via ER stress dysregulation. Preclinical studies explore small molecules targeting UFL1’s ligase activity for ER stress-related diseases, though no clinical drugs are approved yet.