SOX15 is a transcription factor that binds DNA at specific consensus sequences and functions as both a transcriptional activator and repressor 1. In normal physiology, SOX15 is a key regulator of stratified epithelial cell identity, with expression restricted to esophageal and other stratified epithelia where it directly controls esophagus-specific gene transcription 1. SOX15 plays regulatory roles in cell proliferation and differentiation, including myoblast development and skeletal muscle regeneration through transcriptional control of myogenic genes [UniProt annotation supported by functional studies]. In cancer biology, SOX15 functions as a tumor suppressor across multiple malignancies. In esophageal squamous cell carcinoma (ESCC), SOX15 is aberrantly overexpressed, and its inhibition sensitizes cancer cells to paclitaxel through suppression of WNT and NOTCH signaling pathways 2. Similarly, in colorectal and endometrial cancers, SOX15 overexpression inhibits cell proliferation, migration, and invasion while promoting apoptosis, primarily by downregulating the Wnt/β-catenin signaling pathway 3 4. In glioblastoma, SOX15 expression is decreased through circVPS8-mediated degradation, which inhibits ferroptosis and promotes stemness 5. SOX15 expression loss is associated with malignant progression in esophageal adenocarcinoma, where loss of squamous identity promotes intestinal metaplasia 1. These findings establish SOX15 as a potential biomarker for cancer prognosis and therapeutic response.