Abstract: The neuromuscular junction (NMJ) is the peripheral synapse controlling muscle contraction and coordinated movement in a wide variety of animals. In humans, the mature NMJ is the primary target of morphological disassembly and functional decline in several physiological and pathological conditions, such as aging and motor diseases, respectively. Different paradigms of nerve damage in murine models have revealed that the peripheral nervous system bears regenerative abilities leading to functional NMJ recovery; however, this process is often inefficient in humans, likely due to their larger size and differences in the establishment of a still elusive regenerative niche at the NMJ (Zelada et al., 2021). One way to approach this obstacle is to understand the evolution of synaptic contacts, as they can provide novel insights into the fundamental cellular and molecular requirements that were ancestrally involved in the development and regeneration of neuromuscular synapses. Indeed, relevant information on the molecular mechanisms involved in peripheral neural organization and regeneration has been obtained from flies and worms (Richardson and Shen, 2019). The cephalochordates, also known as amphioxus, are a group of non-vertebrate chordate marine animals sharing many genomic and developmental features with the vertebrates. Interestingly, they also share several, although simplified, anatomical structures with vertebrates, including nervous and muscle tissues. Here, we specifically describe the distinctive neuromuscular contacts in amphioxus and briefly discuss how these features could provide valuable information to promote efficient vertebrate NMJ repair.