UEVLD (UEV3) is a human protein containing an N-terminal ubiquitin-conjugating enzyme variant (UEV) domain with 56% identity to Tsg101 and a C-terminal lactate dehydrogenase domain 1. As a catalytically inactive E2 enzyme variant, UEVLD likely functions as a regulatory modulator of ubiquitin signaling, playing intermediate roles in trafficking ubiquitylated cargos and modulating ubiquitin processivity 1. The UEV domain may contain binding pockets similar to Tsg101 1, enabling interaction with ubiquitinated substrates through its ubiquitin-binding capability [GO annotation]. UEVLD is broadly expressed across normal tissues and colon cancer samples 2 and localizes to ESCRT-I complexes and endosomal-lysosomal pathways [GO annotations]. Disease relevance includes associations with papillary thyroid carcinoma, where a novel UEVLD-RET fusion gene was identified in cancer samples 3. UEVLD expression changes occur in mTOR pathway-associated cortical malformations, where altered UEVLD levels may contribute to abnormal cellular adhesion and protein transport affecting cortical development 4. Additionally, UEVLD participates in preeclampsia-associated regulatory networks, with altered lncRNA-UEVLD expression detected in affected endothelial cells 5. These findings suggest UEVLD functions in protein quality control and cellular organization with relevance to developmental and neoplastic pathologies.