Abstract: Amyotrophic lateral sclerosis (ALS) is a rapidly progressing neurodegenerative disease, leading to muscle weakness, paralysis and ultimately death due to respiratory failure. Currently licensed drugs have only very limited effects on slowing down disease progression or biomarkers. Despite numerous successful preclinical analyses, most new drugs fail when translated to clinical trials (Petrov et al., 2017). This is believed to be, in part, due to the multilayer heterogeneity of ALS (e.g., clinical, genetic, and molecular; Tzeplaeff et al., 2024). Studies integrating multi-omic data are still limited, making it difficult to fully understand the biological complexity that characterizes the disease.