Amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD) share remarkably similar cellular and molecular characteristics despite their different clinical manifestations. The study analyzed RNA expression in over 620,000 cells from the motor and prefrontal cortex of 73 donors, revealing nearly identical changes in gene expression in the most vulnerable neurons across both diseases. This suggests potential therapeutic targets for ALS may also be effective for FTLD, and vice versa.