Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration. Recent genetic studies have identified numerous genetic factors contributing to ALS, including mutations in genes related to RNA metabolism, protein homeostasis, and cytoskeletal dynamics. The disease is marked by the accumulation of ubiquitinated inclusions, particularly of the TAR-DNA binding protein (TDP-43), and is associated with non-cell-autonomous mechanisms involving glial cells. The C9ORF72 gene mutation is particularly significant, leading to both gain-of-toxic-function and loss-of-function effects. Therapeutic approaches targeting mutant SOD1 and C9ORF72 are being explored, and recent progress in understanding the molecular biology of ALS offers hope for developing effective treatments.Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by progressive motor neuron degeneration. Recent genetic studies have identified numerous genetic factors contributing to ALS, including mutations in genes related to RNA metabolism, protein homeostasis, and cytoskeletal dynamics. The disease is marked by the accumulation of ubiquitinated inclusions, particularly of the TAR-DNA binding protein (TDP-43), and is associated with non-cell-autonomous mechanisms involving glial cells. The C9ORF72 gene mutation is particularly significant, leading to both gain-of-toxic-function and loss-of-function effects. Therapeutic approaches targeting mutant SOD1 and C9ORF72 are being explored, and recent progress in understanding the molecular biology of ALS offers hope for developing effective treatments.