Nptn, or Neuroplastin, is a cell recognition glycoprotein of the immunoglobulin superfamily. It participates in synapse formation and function, calcium signaling, and is associated with pathways related to learning and memory. It also acts as an obligatory subunit of plasma membrane Ca2+-ATPases (PMCAs), regulating Ca2+ homeostasis [2,5].

In β cell-specific Nptn knockout (KO) mice, Nptn deficiency improved glucose tolerance by increasing insulin secretion and β cell mass, while also enhancing proliferation and mitochondrial numbers in β cells. However, Nptn was shown to induce pro-inflammatory cytokines via the TRAF6-NF-κB axis in β cells [1]. In male Nptn-/-mice, they were infertile due to lack of mounting behavior and low testosterone blood levels, despite normal spermatogenesis and sperm number [3]. In Nptn-/-mice, there was also deafness, hair cell and spiral ganglion cell degeneration, and reduced baseline blood flow in the auditory cortex. Neuroplastin was required for the expression of PMCA 2 in outer hair cells [4].

In conclusion, Nptn plays essential roles in multiple biological processes. Its functions span from regulating insulin secretion and pancreatic islet inflammation, to male fertility and hearing. The use of Nptn KO mouse models has been crucial in revealing its role in diabetes-related pancreatic β-cell functions, male reproductive behavior and infertility, as well as in auditory system development and function.