E3 UFM1-protein ligase 1

UFL1 (E3 UFM1-protein ligase 1) is an E3 ubiquitin-like modifier ligase that catalyzes ufmylation, the covalent attachment of UFM1 to lysine residues on target proteins (UniProt: O94874). This post-translational modification regulates diverse cellular processes including ribosome recycling, DNA damage response, endoplasmic reticulum-associated protein degradation, and immune regulation through substrates such as RPL26, histone H4, MRE11, and PD-1.

UFL1 functions broadly across cellular compartments, with particular relevance to ER stress response and ribosomal function. Its ufmylation activity mediates reticulophagy, promotes 60S ribosome recycling from ER membranes, and regulates T-cell activation. The protein is required for hematopoietic stem cell maintenance and normal hematopoiesis (UniProt: O94874).

In Alzheimer's Disease, UFL1 shows ambiguous regulation across brain subcellular fractions in post-mortem tissue, with a mean log2 fold-change of 0.0175 relative to age-matched controls (Chaparral AD proteomics). This minimal average change masks potential compartment-specific alterations that may reflect disrupted ribosomal function or ER proteostasis in AD pathology.