Neurexophilin 3 (Nxph3) is a specific ligand of synaptic alpha-neurexins, which are crucial for efficient neurotransmitter release. It may act as a locally and temporally regulated neuropeptide-like molecule, presumably in a complex with alpha-neurexins in select neuronal circuits [1].

Gene knockout mouse models have been instrumental in understanding its functions. Nxph3-deficient mice showed no anatomical defects but had functional abnormalities in sensory information processing and motor coordination, such as increased startle response, reduced prepulse inhibition, and poor rotarod performance, indicating its importance in these processes [1]. Also, NXPH3 has been found to support the survival of mouse induced pluripotent stem cell-derived dopaminergic neurons in vitro and in vivo, and its expression was lower in PD patients compared with normal controls, suggesting its potential role in Parkinson's disease cell therapy [2]. In addition, in mesodiencephalic dopaminergic neuronal development, deletion of Tcf4 affected the expression of Nxph3, indicating its involvement in the correct differentiation of mdDA neuronal subsets [3].

In summary, Nxph3 plays essential roles in sensorimotor gating, motor coordination, and the survival of dopaminergic progenitors. The study of Nxph3 knockout mouse models has provided valuable insights into its functions in these biological processes and its potential implications in diseases like Parkinson's disease.