PITX1 is a sequence-specific transcription factor belonging to the paired-like homeodomain family that functions as a developmental regulator and tumor suppressor. As a transcriptional activator, PITX1 binds to gene promoters and regulates transcription through RNA polymerase II 1. PITX1 plays critical roles in anterior structure development, particularly in specifying hindlimb identity and morphogenesis 2. In developmental contexts, PITX1 expression is uniquely restricted to hindlimbs and plays essential roles in corneal epithelial differentiation, where it is activated by the transcription factor RORA to drive limbal stem/progenitor cell differentiation 3. Additionally, PITX1 regulates epithelial cell differentiation and wound healing in oral mucosa, conferring unique keratinocyte identity that enhances migration and repair 1. Pathologically, PITX1 functions as a tumor suppressor. Downregulation of PITX1 expression correlates with progression in cutaneous melanoma, with reduced expression linked to increased tumor thickness, metastasis frequency, and higher cell proliferation 4. Similarly, PITX1 is downregulated in lung cancer, where lower expression associates with higher tumor stages 5. In osteosarcoma, PITX1 suppresses cell proliferation and metastasis by antagonizing STAT3 transcriptional activity, which represses the oncogenic long non-coding RNA LINC00662 6. These findings suggest PITX1 loss promotes malignant progression across multiple cancer types, establishing its importance as a developmental regulator and cancer suppressor.