MCTS1 (MCTS1 re-initiation and release factor) functions as a critical translation regulator that forms a complex with DENR to promote translation reinitiation, a process where ribosomes remain attached to mRNA after terminating translation of upstream open reading frames (uORFs) and resume scanning to initiate downstream translation 1. The MCTS1/DENR complex facilitates two essential mechanisms: dissociation of deacylated tRNAs from post-termination 40S ribosomal complexes and EIF2-independent recruitment of aminoacylated initiator tRNA to ribosomal P sites 1. This regulatory mechanism controls translation of over 150 genes, modulating diverse biological processes including cell cycle regulation and DNA damage signaling 2. Clinically, X-linked recessive MCTS1 deficiency causes immunodeficiency 118, characterized by severe mycobacterial infections due to impaired JAK2 translation, which disrupts IL-23 responses and IFN-γ production by innate-like adaptive T cells 2. MCTS1 also plays oncogenic roles in cancer, particularly triple-negative breast cancer, where it promotes epithelial-mesenchymal transition, cancer stemness, and M2 macrophage polarization through IL-6/IL-6R signaling 3. Additionally, MCTS1 enhances laryngeal squamous cell carcinoma proliferation by stabilizing LIN28B through OTUD6B-mediated deubiquitination 4.