Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder in which upper and lower motor neurons are progressively lost, with survival generally less than 5 years. In >90% of patients, the RNA processing protein TDP-43 mislocalises to the cytoplasm and forms inclusions, driving widespread changes in alternative splicing and gene expression. However, recent research has uncovered heterogeneity in how these cytoplasmic inclusions are distributed and composed. We performed deep RNA sequencing on human postmortem motor cortex tissue comparing two patient cohorts with divergent inclusion profiles (n=13 and 17). Approximately 150 differentially-expressed genes were identified, enriched in synaptic and RNA processing ontologies. Notably, the ALS risk gene UNC13A showed significantly higher intron retention in one group, which may represent a novel mechanism underlying ALS pathology. These results highlight the utility in dissecting patient heterogeneity in ALS.