AbstractSynaptic glycoprotein neuroplastin is involved in synaptic plasticity and complex molecular events underlying learning and memory. Studies in mice and rats suggest that neuroplastin is essential for cognition, as it is needed for long-term potentiation and associative memory formation. Recently, it was found that some of the effects of neuroplastin are related to regulation of calcium homeostasis through interactions with plasma membrane calcium ATPases. Neuroplastin is increasingly seen as a key factor in complex brain functions, but studies in humans remain scarce. Here we summarize present knowledge about neuroplastin in human tissues and argue its genetic association with cortical thickness, intelligence, schizophrenia, and autism; specific immunolocalization depicting hippocampal trisynaptic pathway; potential role in tissue compensatory response in neurodegeneration; and high, almost housekeeping, level of spatio-temporal gene expression in the human brain. We also propose that neuroplastin acts as a housekeeper of neuroplasticity, and that it may be considered as an important novel cognition-related molecule in humans. Several promising directions for future investigations are suggested, which may complete our understanding of neuroplastin actions in molecular basis of human cognition.