The functional analysis of down-regulated genes in clusters 2 and 3 revealed their involvement in transmembrane transport (AQP4, ANXA2, GRIK5, HCN1, HTR2B, SLC24A2), extracellular matrix organization (ANXA2, LTBP4, MATN2, MMP7), and synaptic transmission (GRIK5, HTR2B, SLC24A2), while the up-regulated genes in these clusters were mainly enriched in metabolic processes (ACVR2A, ALAD, ALG14, FZR1, HOXC9, MGAT2, RNF14, SOCS5, ZDHHC3) and protein ubiquitination (CRBN, PCNP, RNF14), supporting the pathogenic role of these processes in ALS [96,97,98,99,100,101,102,103,104,105,106,107] (Figure 4). Here, PCNP is linked to amyotrophic lateral sclerosis.