This lecture delves into the genetics of Amyotrophic Lateral Sclerosis (ALS), focusing on RNA metabolism and the role of proteins like TDP-43 and FUS/TLS. It covers mutations, oligomerization, cytosolic relocalization, stress granules, and the impact of C9orf72 hexanucleotide repeat expansion. The talk explores the formation of toxic dipeptide-repeat proteins, nucleocytoplasmic transport blockade, and potential therapeutic approaches.