The protein superfamily of transmembrane receptor tyrosine kinases (RTKs) are essential components of intercellular signalling pathways necessary for normal cellular regulation. We report the cloning and developmental expression pattern of Nsk2, a novel, structurally distinct mammalian RTK characterised by a putative extracellular region bearing four immunoglobulin-like domains. The Nsk2 locus was mapped to the distal region of mouse chromosome 13 and was found to be expressed preferentially in skeletal muscle amongst adult mouse tissues. Moreover, increased steady-state levels of Nsk2 transcripts were apparent on terminal differentiation of committed skeletal myoblast cell lines in vitro and multiple isoforms of the Nsk2 RTK were identified in skeletal myotube cultures. RNA in situ hybridisation studies of mouse embryos confirmed skeletal myogenesis to be a major site of Nsk2 expression during normal embryogenesis, and identified other likely sites of Nsk2 function in ganglia of the developing peripheral nervous system and various embryonic epithelia, including those of kidney, lung and gut, during fetal development. Taken together, our data suggest normal functions for Nsk2 RTKs in distinctive aspects of skeletal muscle development, neurogenesis and mesenchymal-epithelial interactions during organ formation.