Nerve growth factor (NGF) is involved in the maintenance and growth of specific neuronal populations whereas its precursor, proNGF, shows opposite properties, like being involved in apoptosis. NGF/proNGF imbalance is linked to neurodegeneration. Here, we show that ATP binds to proNGF inducing an overall proNGF shape change, throughout a local conformational rearrangement of the flexible pro-peptide domain. This suggests a functional role for ATP in the modulation of proNGF/NGF physiological homeostasis.