This study investigates the ultrastructural changes in the lower motor system of Twitcher (TWI) mice, a mouse model of Krabbe disease (KD), using transmission electron microscopy (TEM). KD is a neurodegenerative disorder caused by the lack of β3-galactosylceramidase activity and the accumulation of cytotoxic galactosyl-sphingosine in neuronal, myelinating, and endothelial cells. The study focuses on the alterations in the lower motor system at postnatal day 15 (P15) and juvenile P30 stages. At P15, mild effects were observed in motoneuron somata, while severe effects were noted in sciatic nerves and even more severe effects in nerve terminals and neuromuscular junctions at P30. The gastrocnemius muscle also showed atrophy and structural changes at P15. The findings support recent theories of a dying-back mechanism for neuronal degeneration, independent of demyelination, and provide new insights into the progression of KD.This study investigates the ultrastructural changes in the lower motor system of Twitcher (TWI) mice, a mouse model of Krabbe disease (KD), using transmission electron microscopy (TEM). KD is a neurodegenerative disorder caused by the lack of β3-galactosylceramidase activity and the accumulation of cytotoxic galactosyl-sphingosine in neuronal, myelinating, and endothelial cells. The study focuses on the alterations in the lower motor system at postnatal day 15 (P15) and juvenile P30 stages. At P15, mild effects were observed in motoneuron somata, while severe effects were noted in sciatic nerves and even more severe effects in nerve terminals and neuromuscular junctions at P30. The gastrocnemius muscle also showed atrophy and structural changes at P15. The findings support recent theories of a dying-back mechanism for neuronal degeneration, independent of demyelination, and provide new insights into the progression of KD.