The actual cause(s) of most cases of Amyotrophic lateral sclerosis (sporadic ALS; sALS) remain undefined, however, approximately 5-10% of cases are familial (fALS). ALS pathology is characterised by a number of intraneuronal protein deposits including, among others, ubiquitinated round, conglomerate or skein-like inclusions. The composition of ubiquitinated inclusions varies considerably depending on whether the disease is sporadic or familial and the genetics of the familial forms. Both FUS and SOD1 mutations cause ALS with FUS- and SOD1-positive inclusions, respectively. However, most other cases have inclusions positive for TDP-43. Inclusions in sALS have been observed to contain the fALS-associated proteins FUS, optineurin, ubiquilin 2 and p62, in addition to TDP-43. Collectively, these data implicate protein aggregation as an underlying mechanism important to ALS pathology. This study aimed to test whether fALS-associated mutant proteins aggregate via distinct mechanisms. At present we have found, using transient transfections with fALS mutant-GFP fusions, that our mammalian neuronal cell culture model replicates the pathology found in human post-mortem tissue; the co-localisation of SOD1, TDP-43, FUS, p62, ubiquilin 2, optineurin and VAPB to inclusions, with mutual exclusivity between SOD1- and TDP-43 -inclusions. We see differences in the morphology of inclusions between the fALS-mutants, as well as in the timing of co-aggregation with ubiquitin, and differences in co-localisation with dense Htt(ex1)46Q-RFP inclusions. Moreover, we find that while TDP-43-inclusions can be found adjacent to LC3-positive foci (presumably autophagosomes), SOD1-inclusions are not. In addition, our results suggest that microtubule destabilisation diminishes numbers of SOD1-inclusions but not TDP-43- or FUS-inclusions. These data suggest that the properties of inclusions and the pathways through which they form in ALS are distinct between the fALS-mutants. Given the differences in their aggregation pathways, we propose that the commonality between these fALS-mutant genes exists in the widespread dysfunction of proteostasis and not in a single aggregation pathway.