HOXC8 (homeobox C8) is a sequence-specific transcription factor that functions as a developmental regulatory gene providing cells with positional identities along the anterior-posterior axis 1. Beyond developmental roles, HOXC8 has emerged as a critical oncogenic transcription factor across multiple cancer types. In NSCLC, HOXC8 suppresses pyroptotic cell death by negatively regulating caspase-1 (CASP1) expression through HDAC1/2 recruitment to the CASP1 promoter, thereby promoting tumor survival 2. In cervical cancer, HPV16 E7 downregulates miR-23a, which normally targets HOXC8; this axis promotes cell viability and migration 3. HOXC8 also activates NAT10, which catalyzes ac4C modification of FOXP1 mRNA, enhancing glycolytic metabolism and immunosuppression in the tumor microenvironment 4. In intrahepatic cholangiocarcinoma, circSLCO1B3-derived miR-502-5p targets HOXC8 to promote proliferation and metastasis via SMAD3 signaling 5. Colorectal cancer cells overexpressing HOXC8 exhibit enhanced stemness through HOXC8-mediated transcriptional activation of TRIM22, leading to NF-κB pathway potentiation 6. In renal fibrosis, HOXC8 acts downstream of TGF-β-Smad3 signaling as a pro-fibrotic transcription factor recruiting P-TEFb for fibrotic gene expression, with therapeutic implications for methionine restriction 7. Conversely, in hair follicle development, Hedgehog signaling activates HOXC8-containing regulatory networks that promote hair growth 1.