UFM1 specific peptidase 1 (UFSP1)

UFM1 specific peptidase 1 (UFSP1) is an **active cysteine protease enzyme** involved in the post-translational modification pathway known as UFMylation, which is a ubiquitin-like system unique to metazoans and plants. UFSP1 is responsible for the **maturation of UFM1** (ubiquitin-fold modifier 1) by cleaving its C-terminal Ser-Cys dipeptide to expose the critical glycine residue required for subsequent conjugation to substrate proteins. Additionally, UFSP1, alongside UFSP2, catalyzes the removal of UFM1 from protein substrates, a process termed **de-UFMylation**. UFSP1 is widely expressed (though at a lower level than UFSP2 in humans), localizes primarily in the cytosol, and initiates translation from an upstream CUG codon, not the canonical AUG, to produce the active protease form[1][3]. The UFMylation pathway is **implicated in cellular processes such as erythropoiesis, endoplasmic reticulum (ER) homeostasis, and response to stress**, and deficiencies or mutations in UFMylation components—including *UFSP1*—are associated with embryonic lethality in mice and a range of human diseases, including neurological and skeletal disorders, and cancer[1][3]. UFSP1 is not currently known to be directly targeted by approved drugs, nor is it a routine clinical biomarker. No common drugs or clinically used UFSP1-targeting inhibitors or activators are reported, nor are notable safety or toxicity issues specifically described for UFSP1 modulation as of the cited research[1][3].

Other names

Ufm1-specific protease 1UFSP1UfSP1UFSPufm1-specific protease 1UFM1 specific peptidase 1 (inactive)inactive Ufm1-specific protease 1

Cleavage of the C-terminal Ser-Cys dipeptide from the UFM1 precursor to generate mature UFM1[1][3], Removal of UFM1 from conjugated protein substrates (de-UFMylation)[1][3]