Small proline-rich protein 3 (SPRR3)

Small proline-rich protein 3 (SPRR3) is a protein encoded by a single gene on chromosome 1q21-q22, structurally characterized by proline-rich repeats and acting as a "cross-bridging component" in the cornified envelope of stratified epithelial cells[2]. SPRR3 is crucial for epithelial barrier integrity and proper keratinocyte differentiation; its dysregulation is linked to inflammatory skin diseases and altered during wound repair. SPRR3 displays a context-dependent role in cancer: its loss is associated with esophageal squamous cell carcinoma initiation, while its upregulation in several solid tumors enhances proliferation, invasion, and aggressiveness by activating key signaling pathways like AKT, MEK/MAPK, and NF-κB[1]. Environmental stressors, such as particulate pollution, can induce SPRR3, impacting cellular structures like primary cilia[1]. Mechanosensitive in vascular cells, SPRR3 is upregulated by cyclic strain and integrin-mediated signaling, implicating it in atherosclerosis. SPRR3 also modulates immune responses, as evidenced by roles in allergic inflammation and broad associations with disease and tissue-specific expression[1]. Emerging evidence suggests SPRR protein family members may have antimicrobial functions, but SPRR3’s specific activity has not been strongly characterized in this context[5].

Other names

SPRR3Cornifin betaEsophagin22 kDa pancornulinSmall proline-rich protein 3SPRC

No specific mechanism of action as SPRR3 is not a direct drug target. Contextually, drugs impacting keratinocyte differentiation, inflammation, or signaling pathways (AKT, MEK/MAPK, NF-κB) could modulate SPRR3 expression as a downstream effect[1].