Abstract: Neurons are highly polarized cells with axons reaching over a meter long in adult humans. To survive and maintain their proper function, neurons depend on specific mechanisms that regulate spatiotemporal signaling and metabolic events, which need to be carried out at the right place, time, and intensity. Such mechanisms include axonal transport, local synthesis, and liquid–liquid phase separations. Alterations and malfunctions in these processes are correlated to neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS). ALS is a fast-progressing fatal motor neuron disease pathologically characterized by muscle atrophy, neuromuscular junction degeneration, and eventually, motor neuron death (Rothstein, 2009). While the precise mechanisms underlying ALS pathogenesis remain elusive, TAR DNA binding protein 43 (TDP-43) mislocalization and aggregation play a key role in the disease process (Buratti and Baralle, 2009; Lee et al., 2012; Piol et al., 2023). Concurrently, disruptions in axonal transport, and alterations in local synthesis, which are vital for neuronal function, have also been observed in ALS. Understanding the bidirectional interplay between TDP-43 aggregation and axonal transport/local synthesis events holds promise for elucidating ALS pathology and advancing therapeutic strategies.