E3 protein ligase that mediates ufmylation, the covalent attachment of the ubiquitin-like modifier UFM1 to lysine residues on target proteins, and which plays a key role in reticulophagy (also called ER-phagy) induced in response to endoplasmic reticulum stress. In response to endoplasmic reticulum stress, recruited to the endoplasmic reticulum membrane, and mediates ufmylation of proteins, thereby promoting reticulophagy of endoplasmic reticulum sheets. Ufmylation-dependent reticulophagy inhibits the unfolded protein response (UPR). Ufmylation in response to endoplasmic reticulum stress is essential for processes such as hematopoiesis, blood vessel morphogenesis or inflammatory response. Also involved in the response to DNA damage: recruited to double-strand break sites following DNA damage and mediates monoufmylation of histone H4 (By similarity). Required for hematopoietic stem cell function and hematopoiesis (By similarity). Recruited to double-strand breaks following DNA damage. Belongs to the UFL1 family.