HOXB9 (homeobox B9) is a sequence-specific transcription factor that plays diverse roles in cancer biology, with context-dependent tumor suppressor and oncogenic functions. In lung adenocarcinoma, HOXB9 promotes metastasis through WNT-dependent signaling and upregulates KRAS expression, with higher levels associated with poor prognosis 12. The protein's stability is regulated by AMPK-mediated phosphorylation at T133, which promotes Praja2-mediated degradation 2. Conversely, in pancreatic cancer, HOXB9 functions as a tumor suppressor by blocking cell cycle progression through upregulating RBL2 and inhibiting c-Myc, with DNMT1-mediated promoter methylation reducing its expression 3. In endometrial cancer, oleic acid stabilizes HOXB9 by preventing its degradation, leading to ODC1 stabilization and polyamine accumulation that promotes tumor growth 4. HOXB9 also regulates ferroptosis through transcriptional control of SLC7A11, with cold atmospheric plasma enhancing PCAF-mediated HOXB9 acetylation and subsequent protein degradation 5. Additionally, HOXB9 expression is lost during renal medullary carcinoma transformation, contributing to ferroptosis resistance 6. These findings highlight HOXB9's complex regulatory mechanisms and its potential as both a therapeutic target and prognostic marker across multiple cancer types.