Nature Reviews Neuroscience, Published online: 06 July 2026; doi:10.1038/s41583-026-01057-x Motor neuron disorders involve complex interactions between multiple CNS cell types, which are challenging to model in 2D in vitro conditions. Frizzi and colleagues describe recent advances in induced pluripotent stem cell-based 3D (organoid) models of the spinal cord and neuromuscular junction, and outline their application in the investigation of disease mechanisms.