S100P is a small calcium-binding protein (10.4 kDa) that functions as a calcium sensor and cellular signaling regulator 1. Intracellularly, S100P interacts with proteins like ezrin and calcyclin-binding protein to regulate cytoskeletal dynamics and microvilli formation 1. Extracellularly, S100P activates the receptor for advanced glycation end products (RAGE), stimulating cell proliferation and signaling cascades 2. Recent mechanistic studies reveal S100P promotes ferroptosis resistance in hepatocellular carcinoma by facilitating lysosomal degradation of acetyl-CoA carboxylase 1 (ACC1) through RAB5C-mediated selective autophagy, thereby rewiring lipid metabolism 3. In non-small cell lung cancer, RBMS1 coordinates with YTHDF1 to enhance S100P translation, accelerating metastasis 4. S100P is significantly upregulated across multiple cancers including breast, pancreas, lung, and ovarian carcinomas, where it associates with poor prognosis, metastasis, drug resistance, and invasion 12. S100P also serves as a diagnostic biomarker for sepsis, demonstrating differential expression between septic patients and healthy controls with high clinical diagnostic value 5. Transcriptional regulation involves SMAD, STAT/CREB, and SP/KLF binding sites, with hypomethylation contributing to elevated expression 2. Given its cancer-specific expression pattern and therapeutic potential, S100P represents a promising druggable target for cancer and inflammatory disease treatment.