NKX3-2 is a transcriptional repressor belonging to the NK homeobox gene family with diverse developmental and pathological roles. Developmentally, NKX3-2 acts as a negative regulator of chondrocyte maturation 1 and is essential for axial skeleton patterning, particularly vertebral centrum and intervertebral disc development 2. It also regulates gastric mesenchyme development and antral-pyloric morphogenesis 2. Beyond skeletal development, NKX3-2 has emerged as a multifunctional transcription factor in disease contexts. In ovarian cancer, NKX3-2 promotes cell migration by suppressing autophagy through HDAC6-mediated lysosome repositioning 3, and represents a negative prognostic factor when highly expressed and not subject to P53-induced autophagy degradation 4. In T-cell acute lymphoblastic leukemia, NKX3-2 is aberrantly activated in 18% of pediatric patients, deregulating BMP and MAPK signaling to suppress T-cell differentiation 5. In immune function, NKX3-2 maintains ADGRB3 expression in T cells through non-muscle myosin II signaling, reducing traction force and anti-tumor cytotoxicity 6. Conversely, in retinal pigment epithelium, NKX3-2 provides protective effects by suppressing inflammation and necroptosis through RIP3 degradation 7. NKX3-2 is currently in clinical trials for osteoarthritis gene therapy 8.