The neuromuscular junction (NMJ) is crucial for understanding the fundamentals of synaptic transmission and activity. Various modulators operate within neuronal circuits, from sensory to motor neurons, to influence synaptic transmission at the NMJ. This study sheds light on the regulation of sensory-evoked cholinergic neurotransmission at motor neurons orchestrated by CASY-1, the mammalian calsyntenin orthologue. We report that the increased excitation-inhibition (E-I) ratio at the NMJ in