LHX2 is a LIM homeobox transcription factor that functions as a DNA-binding transcriptional regulator with critical roles across multiple developmental and disease contexts. It acts as a transcriptional activator controlling cell differentiation in lymphoid and neural cell types 1, with essential functions in forebrain, eye, olfactory system, and liver development 2. During limb development, LHX2 is regulated by Fgf and Wnt signaling through tissue-specific cis-regulatory modules and coordinates proliferation and patterning 3. In disease contexts, LHX2 haploinsufficiency causes variable neurodevelopmental disorders characterized by developmental delays, autism spectrum disorder, intellectual disability, and microcephaly through loss-of-function mechanisms 4. In hepatic disease, HSC-specific LHX2 expression promotes liver regeneration while inhibiting fibrosis by upregulating pro-regenerative factors like HGF and blocking TGF-β signaling via SMAD6 upregulation 5. Conversely, LHX2 drives aggressive tumor phenotypes: in prostate cancer, it forms a positive feedback loop with glycolytic metabolism and histone lactylation to promote neuroendocrine transdifferentiation 6, while in medulloblastoma, it enhances oncogenic BMP signaling, promotes stemness, and increases chemoresistance and metastatic potential 7. In cholangiocarcinoma, fibroblast-specific LHX2 expression contributes to tumor-promoting microenvironment remodeling 8.