YPEL5 is a component of the CTLH E3 ubiquitin-protein ligase complex that mediates proteasomal degradation of specific substrates. As part of the GID/CTLH complex, YPEL5 selectively accepts ubiquitin from UBE2H and targets proteins for degradation, including the transcription factor HBP1 1. YPEL5 also functions as a negative regulator within the complex: it inhibits WDR26-mediated ubiquitylation of NMNAT1, thereby modulating metabolic enzyme turnover and prodrug sensitivity 2. During cell division, YPEL5 localizes to centrosomes, spindle poles, the mitotic spindle, and midbody, indicating involvement in cell cycle progression 3. YPEL5 interacts with RanBPM and RanBP10 proteins, which are Scorpin family members also involved in CTLH complex function. Knockdown of YPEL5 inhibits cell proliferation 3. Clinically, YPEL5 demonstrates pro-apoptotic function: its expression enhances sensitivity to DNA-damaging agents (UV radiation, MMS, CPT) through mitochondria-dependent apoptotic pathways 4. Conversely, the GID/CTLH complex (including YPEL5) suppresses host anti-microbial responses; knockout macrophages show enhanced autophagy and bacterial growth restriction 5. In bladder cancer, YPEL5 shows protective association with reduced expression in tumors, and its overexpression decreases cancer cell proliferation and invasion 6. YPEL5 expression also increases during erlotinib treatment of EGFR-mutant lung cancer 7.