Regucalcin (RGN), also known as senescence marker protein-30 (SMP30), is a calcium-binding protein with multifaceted cellular functions. Structurally, RGN possesses gluconolactonase activity and can bind zinc ions, modulating intracellular calcium homeostasis and regulating calcium-dependent cellular processes and enzyme activities 1. RGN exerts calcium signaling inhibition through its potent regulatory mechanisms 2. Clinically, RGN emerges as a significant biomarker across multiple disease contexts. In prostate cancer, elevated RGN expression correlates with longer recurrence-free and overall survival, promoting tumor dormancy through p38 MAPK activation, ERK suppression, FOXM1 inhibition, and exosomal miR-23c-mediated angiogenesis suppression 3. In lung squamous cell carcinoma (LUSC), RGN is downregulated in tumors and associated with improved prognosis; its expression modulates immune infiltration patterns including T cells, macrophages, and neutrophils, suggesting utility for predicting immunotherapy efficacy 2. Beyond cancer, RGN is recognized as a high-priority biomarker candidate for frailty assessment in aging populations, reflecting its role in calcium homeostasis—a hallmark aging pathway 4. These findings establish RGN as both a fundamental regulator of calcium signaling and a clinically relevant prognostic indicator with implications for cancer recurrence prediction and age-related disease assessment.