KRT33B (keratin 33B) is a type I keratin intermediate filament protein primarily expressed in hair follicle cortex tissue during the hair cycle 1. As a structural component of epithelial tissues, KRT33B participates in intermediate filament organization and cytoskeletal architecture 1. Beyond its canonical role in hair development, KRT33B has emerged as a significant biomarker in human malignancies. In tongue squamous cell carcinoma (TSCC), KRT33B expression is differentially regulated and contributes to a validated three-gene prognostic signature that independently predicts patient survival with high accuracy (concordance index: 0.851) 2. Similarly, in head and neck squamous cell carcinoma (HNSCC), KRT33B functions as both a diagnostic and prognostic biomarker; when combined with ACADM and C14orf34, it achieves 92% sensitivity and 93% area under the curve for disease detection 3. In gliomas, KRT33B serves as a cooperative prognostic biomarker for low-grade glioma, subject to both transcriptional and post-transcriptional regulation by long non-coding RNAs 4. These findings suggest KRT33B dysregulation is associated with carcinogenesis and tumor progression, making it a promising therapeutic target and prognostic indicator across multiple cancer types.