MCTS2 (MCTS family member 2) is an imprinted retrogene located on chromosome 20 that functions in translation re-initiation and appears to have epigenetic regulatory roles. Primary Function: MCTS2 encodes a DENR partner protein that promotes ribosomal re-initiation at upstream open reading frames (uORFs), allowing resumed scanning and downstream translation initiation after termination at uORFs 1. This function parallels its homolog MCTS1-DENR but operates through distinct mechanisms independent of broader gene regulation controlled by eIF2D 1. Mechanism: MCTS2 participates in the formation of translation preinitiation complexes during the re-initiation process 1. The gene is paternally expressed and undergoes promoter methylation during oogenesis as an imprinted locus, reflecting its origin as a retrogene derived from X chromosome 20 2. Disease and Clinical Relevance: MCTS2 methylation status serves as a sensitive biomarker for environmental exposure and health outcomes. Alterations in MCTS2 DNA methylation correlate with fine particulate matter (PM2.5) exposure and constituent metals, with implications for cancer pathways 3. Changes in MCTS2 imprinting methylation predict hippocampal volume changes and white matter hyperintensities with aging 4. Additionally, MCTS2 methylation aberrations are identified in patients with intellectual disability and imprinting disorders 5. Dysregulation of MCTS2 imprinting control regions occurs when TET3-mediated DNA demethylation is compromised in neural progenitor cells 6.