Bo Pang, Huan Sun, Mingyu Ouyang, Cong Hu
Secreted Phosphoprotein 1 (SPP1) is a multifaceted matricellular glycoprotein that mediates diverse biological processes via integrin and CD44 receptor signaling. While its profound contributions to tumor progression and metastasis are extensively documented, emerging evidence underscores its pivotal roles across diverse non-cancerous conditions, including pregnancy-related complications, fibrotic diseases and neurological disorders. Crucially, SPP1 exhibits functional pleiotropy, orchestrating angiogenesis and epithelial-mesenchymal transition, while modulating immunosuppression. These collective actions drive disease progression, establishing SPP1 as a compelling therapeutic target. This review synthesizes current understanding of SPP1 biology, highlighting mechanistic insights imperative for translating its therapeutic potential into safe, precision-targeted interventions against diverse SPP1-driven pathologies.