NRG1

Neuregulin 1 (NRG1) is a gene that encodes a member of the neuregulin family of signaling proteins. The NRG1 protein acts as a ligand for the ErbB family of receptor tyrosine kinases, with signaling primarily through ErbB3 and ErbB4, and often in collaboration with ErbB2. This signaling regulates a variety of developmental and physiological processes in the nervous system, heart, and other tissues.

The NRG1 gene is complex and produces multiple isoforms through alternative promoters and splicing. Isoforms are typically categorized into several types, most notably I–III. Some isoforms are secreted forms, while others are membrane-bound. All major isoforms contain an epidermal growth factor (EGF)-like domain that binds ErbB receptors, typically after proteolytic processing that releases the EGF-like segment for receptor activation.

NRG1 plays a key role in neural development and function, influencing neuronal differentiation, synaptic plasticity, and the development and maintenance of myelinating glia such as Schwann cells. In the cardiovascular system, neuregulin-1 signaling contributes to heart development and adaptive responses in adulthood. Additional roles have been investigated in bone, mammary gland development, and peripheral nerves, reflecting its broad signaling potential.

Clinical significance attributed to NRG1 includes associations with neuropsychiatric conditions and cancer. Genetic variation in NRG1 has been linked in some studies to schizophrenia risk, though findings are not entirely consistent across populations. In oncology, certain NRG1 gene fusions or overexpression can drive ErbB signaling in subsets of lung cancers, prompting research into targeted therapies that disrupt NRG1-ErbB signaling. Further research continues to clarify its roles and therapeutic potential.