Mitochondrial calcium (Ca2+) uptake through the mitochondrial Ca2+ uniporter (mtCU) complex is essential for maintaining cellular bioenergetics and Ca2+ homeostasis. The activity of mtCU is tightly regulated by MICU1, an intermembrane space protein that prevents Ca2+ entry at low cytosolic Ca2+ concentrations and promotes cooperative activation at higher levels. Human loss of function mutation of MICU1 has been linked to skeletal muscle myopathy, motoric impairment, fatigue, and learning difficulties. In mice, we established that neuronal MICU1 deficiency is associated with motoric and learning disabilities and motor neuron loss, and that MICU1 loss in skeletal muscle leads to muscular atrophy; however, the mechanistic connection between neuronal MICU1 loss and muscle atrophy remains unresolved. In this study, we examined the impact of neuronal MICU1 deficiency on neuromuscular junction (NMJ) integrity and muscle atrophy following chronic constriction injury (CCI) of the sciatic nerve. Our results show that MICU1 deficiency leads to underdeveloped, densely packed neuromuscular junctions (NMJs) in embryonic day 18 (E18) pups, without significant changes in average plaque volume, indicating impaired synaptic maturation. Because whole-body MICU1 knockout mice do not survive postnatally, we employed a chronic constriction injury (CCI) model to assess the impact of neuronal MICU1 loss on muscle atrophy. Following CCI of the sciatic nerve in adult neuronal MICU1 KO mice, we observed enhanced tactile allodynia. Although the reduction in gastrocnemius muscle mass was comparable between wild-type (WT) and KO mice relative to their contralateral sides, MICU1 KO muscles exhibited marked structural alterations. These included decreased muscle fiber area and increased interstitial space within the tibialis anterior (TA) muscle, as revealed by H&E staining. Furthermore, these morphological changes were accompanied by altered expression of mtCU subunits and differential regulation of genes associated with muscle degeneration and regeneration at 18 days post-CCI. Collectively, our findings uncover a pivotal role for neuronal MICU1 in maintaining neuromuscular junction integrity, muscle architecture, and sensory function through mitochondrial Ca2+ homeostasis, providing mechanistic insight into the neuromuscular and sensory pathology associated with MICU1 deficiency.