Neurexophilin-1 (NXPH1)

Neurexophilin-1 is a secreted neuropeptide-like glycoprotein encoded by the NXPH1 gene. Structurally, it contains a variable N-terminal domain, a conserved N-glycosylated central domain, a linker, and a cysteine-rich C-terminal region. The mature protein is produced by proteolytic processing after synthesis. Neurexophilin-1 forms a high-affinity complex with alpha-neurexin receptors, promoting synapse formation, maturation, and maintaining synaptic integrity, particularly in inhibitory neurons. It critically regulates short-term synaptic plasticity and the configuration and function of GABAergic synapses. Outside the brain, NXPH1 can suppress hematopoietic progenitor cell proliferation via antagonistic binding to NRXN1α, contributing to immune regulation and clinical observations in transplantation and cancer prognosis. Genetic and epigenetic alterations in NXPH1 have been implicated as biomarkers or contributory factors in neuropsychiatric disorders and breast cancer. The protein, therefore, bridges synaptic development and immune modulation, with potential relevance as a therapeutic and diagnostic target.

Other names

Neurexophilin 1NXPH1NPH1Nbla00697neurexophilin-1

Acts as a protein ligand for alpha-neurexin receptors, modulating their interactions at the synaptic cleft. Regulates synaptic plasticity by stabilizing GABA_B and GABA_A receptors at synapses. Inhibits hematopoietic progenitor cell proliferation via binding NRXN1α.