Genetic ablation of Fezf2 resulting in the complete absence of Layer 5 projection neurons in an ALS mouse models achieved by crossbreeding Fezf2 KO mice with SOD1G93A mice paradoxically delayed disease onset and progression [53], further highlighting the specificity of Fezf2 to identify vulnerable UMNs within the diverse architecture of Layer 5 in ALS. Here, FEZF2 is linked to amyotrophic lateral sclerosis.