Roberto Paparella, Francesca Pastore, Lavinia Marchetti, Arianna Bei, Irene Bernabei, Norma Iafrate, Vittorio Maglione, Marcello Niceta, Anna Zambrano, Mauro Celli, Marco Fiore, Ida Pucarelli, Luigi Tarani
Calcium ions (Ca2+) serve as universal second messengers regulating endocrine, neuronal, and metabolic processes. In children and adolescents, tight calcium signaling control is crucial for growth, hormone homeostasis, neuromuscular function, and neurodevelopment. Disruptions in Ca2+-dependent pathways—whether genetic, metabolic, or acquired—underlie a spectrum of pediatric endocrine diseases often presenting with neurological manifestations This review summarizes calcium’s roles in hormone secretion, parathyroid and vitamin D metabolism, and neuronal excitability, and discusses monogenic and metabolic disorders affecting calcium sensing and signaling, including CASR, GNA11, AP2S1, STIM1, and ORAI1 mutations. Diagnostic challenges, therapeutic strategies, and future directions for precision medicine in pediatric neuroendocrinology are highlighted, emphasizing early recognition and improved clinical outcomes.