SPRR1B (small proline-rich protein 1B) functions as a multifaceted protein involved in epithelial differentiation, wound healing, and cell cycle regulation. Its primary role involves keratinocyte differentiation and cornified envelope formation, where it serves as a cross-linked envelope protein that becomes incorporated into the insoluble envelope beneath the plasma membrane through transglutaminase-mediated cross-linkage 1. SPRR1B demonstrates critical importance in wound healing, particularly in oral mucosa, where STAT3-activated SPRR1B+ keratinocytes are abundant in unwounded tissue and facilitate rapid mucosal repair through enhanced keratinocyte migration 2. The protein also functions as a cell cycle regulator, promoting entry into the G0 phase and inducing tetraploidy when overexpressed 3. Clinically, SPRR1B serves as a biomarker across multiple diseases. It shows diagnostic potential in psoriasis, where its expression correlates with immune cell infiltration patterns 4, and in pterygium pathogenesis 5. In cancer contexts, SPRR1B functions as both a prognostic marker and therapeutic target, with elevated expression associated with poor outcomes in lung adenocarcinoma through MAPK pathway activation 6, while also being identified as part of cancer stemness signatures linked to immunotherapy resistance 7.