Topic: UFMylation

UFM1 is an understudied ubiquitin-like modifier. Like ubiquitin, UFM1 is covalently conjugated to substrate proteins. The conjugation of UFM1 (UFMylation) is reversible, and this is mediated by UFSP2. UFMylation has been linked to important biological pathways such as the DNA damage response, the unfolded protein response, and autophagy. UFMylation is also crucial for healthy brain development, however a role of UFM1 for age-related brain diseases such as Alzheimer’s disease (AD) has not been established. Considering that pathological tau plays a critical role for AD, and has a physiological r

Neurodevelopmental disorders (NDDs) have a highly heterogeneous etiology but share dysfunctional molecular pathways whose characterization is necessary for therapy development. Recently, NDDs have been linked to defects in UFMylation, a post-translational protein modification that involves the covalent and reversible attachment of UFM1 to targets via the orchestrated action of specific enzymes. Interestingly, mutations in the human Ufm1 gene or in genes encoding UFM1-conjugating enzymes have been associated with NDDs. These mutations all cause reduced UFMylation in the brain, providing strikin