SBSN (suprabasin) is a secreted protein originally identified as a component of stratified epithelial tissues, particularly expressed in the basal layer of stratified epithelium 1. The protein exists in multiple isoforms that function as secreted signaling molecules, though their precise physiological roles remain poorly understood 1. SBSN plays critical roles in epidermal barrier function, where decreased expression leads to aberrant keratinocyte differentiation, increased apoptosis, and compromised stratum corneum formation 2. The protein demonstrates anti-apoptotic activity and promotes keratinocyte proliferation 2. SBSN can be processed into bioactive peptides that exhibit diverse functions, including appetite suppression, locomotor activity modulation, and proinflammatory cytokine stimulation via NF-κB activation 3. In cancer contexts, SBSN functions as an oncogene promoting tumor progression through multiple mechanisms. It enhances gastric cancer liver metastasis by activating hepatic stellate cells through EGF/EGFR signaling and subsequent CCL2/CCR2/JAK2 pathways 4. In glioma, SBSN is transferred via extracellular vesicles and activates NF-κB signaling through ANXA1-dependent ubiquitination of NEMO, promoting tumor aggressiveness 5. SBSN expression correlates with poor prognosis across multiple cancer types, including esophageal carcinoma, glioblastoma, and endometrial cancer 16.