Extracellular signal-regulated kinases 1 and 2 regulate neuromuscular junction and myofiber phenotypes in mammalian skeletal muscle

•ERK1/2 signaling regulates neuromuscular synapse-specific transcription.•ERK1/2 signaling regulates acquisition and maintenance of slow myofiber phenotype.•ERK1/2 signaling may control muscle progenitor role after nerve injury and aging. The neuromuscular junction is the synapse between a motor neuron of the spinal cord and a skeletal muscle fiber in the periphery. Reciprocal interactions between these excitable cells, and between them and others cell types present within the muscle tissue, shape the development, homeostasis and plasticity of skeletal muscle. An important aim in the field is to understand the molecular mechanisms underlying these cellular interactions, which include identifying the nature of the signals and receptors involved but also of the downstream intracellular signaling cascades elicited by them. This review focuses on work that shows that skeletal muscle fiber-derived extracellular signal-regulated kinases 1 and 2 (ERK1/2), ubiquitous and prototypical intracellular mitogen-activated protein kinases, have modulatory roles in the maintenance of the neuromuscular synapse and in the acquisition and preservation of fiber type identity in skeletal muscle.