MEIS2 (Meis homeobox 2) is a homeobox transcription factor that plays critical roles in transcriptional regulation across multiple biological contexts. The protein functions primarily by forming complexes with HOX and PBX proteins to regulate target gene expression 1. MEIS2 has been identified as an endogenous substrate of the CRL4(CRBN) E3 ubiquitin ligase complex, suggesting post-translational regulation of its activity 1. In neuroblastoma, MEIS2 acts as a master transcription factor alongside MYCN and HAND2, forming complexes that establish super-enhancers to drive oncogene expression and maintain cellular proliferation 2. The protein demonstrates tissue-specific functions, including regulation of BACE1 expression in Alzheimer's disease pathogenesis, where elevated MEIS2 levels contribute to amyloid plaque formation 3. In liver aging, MEIS2 drives IL-1α expression in senescent liver sinusoidal endothelial cells, promoting inflammatory responses and ischemia-reperfusion injury 4. Clinically, MEIS2 variants are associated with syndromic intellectual disability, including cleft palate and cardiac defects 5. The gene also plays roles in leukemia, where NUP98-MEIS2 fusions contribute to disease phenotypes through direct regulation of differentiation-related genes 6. MEIS2 depletion studies in neuroblastoma reveal its involvement in cell cycle regulation and DNA repair pathways 7.