Abstract: The main function of neurons is information transmission in the form of action potentials. To fulfill this duty, neurons are connected functionally with each other via synapses, the microscopic structures where specialized molecular machinery is strategically placed to release and receive neurotransmitters and to generate and extinguish calcium (Ca2+) signals. These synaptic molecular components are highly dynamic and they influence each other to confer structural and functional adaptability (plasticity) to neuronal communication (Biederer et al., 2017). Recently, neuroplastin (Np), a cell recognition molecule, has emerged to play diverse neuronal functions including synapse formation, spine structure, Ca2+ signal regulation, excitatory/inhibitory balance, and synaptic plasticity. Evidence from different labs has converged to form a coherent picture; however, the uncovered mechanisms may represent only the tip of Np’s iceberg. Many questions remain to be answered. For example, why do neurons need two Np isoforms? How do Np isoforms contribute to Ca2+ signal regulation and synaptic plasticity?