SLURP1 encodes a secreted protein that functions as a multifaceted regulator of cellular homeostasis and immune responses. The protein serves as an allosteric inhibitor of α7 nicotinic acetylcholine receptors, modulating calcium signaling and cellular proliferation 1. In skin physiology, SLURP1 is essential for maintaining keratinocyte differentiation and structural integrity, with its loss causing palmoplantar keratoderma through disruption of ER-based mechano-resistance mechanisms involving SERCA2b calcium pumps 2. The protein exhibits significant anti-tumor activity across multiple cancer types, including colorectal and bladder cancers, by inhibiting cell proliferation, inducing cell cycle arrest at G1/S interface, and modulating inflammatory responses through NF-κB signaling 34. SLURP1 also functions as a protective antioxidant factor in corneal epithelium, upregulating antioxidant enzymes and suppressing ROS accumulation to maintain redox homeostasis 5. Disease associations include autosomal recessive Mal de Meleda from loss-of-function mutations and newly identified autosomal dominant progressive symmetric erythrokeratoderma from signal peptide variants that exhibit dominant-negative effects 67. The protein's diverse functions position it as both a therapeutic target and biomarker for cancer prognosis.