PELO (pelota mRNA surveillance and ribosome rescue factor) is a core component of the Pelota-HBS1L complex that recognizes and rescues stalled ribosomes as part of the No-Go Decay (NGD) pathway 1. The complex specifically engages ribosomes stalled at the 3' end of mRNAs by destabilizing mRNA within the ribosomal channel 2. After the SKI complex extracts mRNA from stalled ribosomes, PELO-HBS1L recruits ABCE1 to catalyze ribosomal disassembly and trigger degradation of damaged mRNAs 3. Structurally, PELO functions as a decoding factor paired with the GTPase Hbs1L, exploiting ribosomal plasticity to remodel the decoding center and coordinate distinct recognition mechanisms 4. Beyond translational quality control, PELO has emerged as a catalytic factor for NOD-like receptor (NLR) inflammasome assembly, activating NLR ATPase activity to enable oligomerization independent of its ribosomal functions 5. In mitochondrial contexts, PELO participates in PINK1-regulated mitophagy signaling 6. Clinically, PELO represents a synthetic lethal therapeutic target in cancers with SKI complex destabilization, including 9p21.3-deleted and microsatellite instability-high (MSI-H) tumors, where PELO inhibition induces the unfolded protein response and tumor growth inhibition 78. Additionally, PELO promotes prostate cancer progression through facilitating PLK1-induced Smad4 degradation 9.