SOX21 is a transcription factor that plays critical roles in cellular differentiation and tissue development across multiple organ systems. In intestinal stem cells, SOX21 functions as part of a negative feedback loop with PPARs to regulate peroxisome dynamics during gut regeneration, where it promotes peroxisome elimination through pexophagy while repressing PPAR expression 1. SOX21 is essential for proper lung epithelial differentiation and repair, working alongside SOX2 to control cell lineage specification during lung development 2. In the nervous system, SOX21 acts as a tumor suppressor in glioma by negatively regulating SOX2 expression, with forced SOX21 expression inducing apoptosis in glioma cells 3. Additionally, SOX21 serves as a prognostic marker in glioblastoma, where it contributes to patient survival prediction models 4. In ocular development, SOX21 dysregulation is linked to congenital microcoria, where ectopic expression disrupts iris development and affects intraocular pressure regulation through TGFB2 signaling 5. The gene's antisense transcript SOX21-AS1 shows aberrant methylation patterns in various cancers, with hypermethylation leading to reduced expression in oral cancer 6 but hypomethylation promoting overexpression in cervical cancer 7.