Recent advances in understanding the molecular mechanisms of amyotrophic lateral sclerosis (ALS) have enabled the translation of novel research findings into clinical practice, including gene therapy approaches. The field has also seen significant improvements in assistive technologies, allowing for more personalized supportive and symptomatic care. This review summarizes recent studies on ALS pathogenesis, clinical trial results, and future directions for improving clinical management. ALS, a severe motor neuron disease, involves both upper and lower motor neurons and is influenced by genetic and environmental factors. Recent studies confirm that ALS incidence is highest in Europe, with increasing trends in Ireland, Scotland, and parts of Italy. In Asia, while overall incidence is lower than in Europe and North America, the prevalence is second only to that of Western Europe, possibly due to genetic differences. The sex ratio in ALS is slightly higher in males, though recent studies suggest a more balanced ratio. The role of sex hormones, environmental exposure, and sex chromosomes may contribute to this difference. Over 40 genes have been associated with ALS, with SOD1, C9orf72, TARDBP, and FUS being the most common. The C9orf72 hexanucleotide repeat expansion is the most common genetic cause in European familial ALS, accounting for over 30% of cases. Recent studies have identified additional genes, such as TBK1, NEK1, and DNAJC7, as potential ALS-related genes. Haploinsufficiency is a shared mechanism among several ALS-related genes, and recent studies have identified new genetic risk factors, such as SUMO4 haploinsufficiency. Environmental factors, including smoking, alcohol consumption, and occupational exposures, have been associated with ALS risk. However, age, male gender, and family history remain the most well-established risk factors. Physical activity and head trauma may also play a role, though the relationship is complex and requires further study. ALS exhibits significant clinical and phenotypic heterogeneity, with various subtypes such as bulbar, flail arm, and respiratory onset ALS. Cognitive and behavioral changes are common in up to half of ALS patients, with some cases meeting criteria for frontotemporal dementia (FTD). These changes can significantly impact patient survival, quality of life, and caregiver burden. Neuroimaging techniques have advanced, providing insights into ALS pathogenesis and progression. Structural and functional imaging have shown early involvement of the corticospinal tract and other brain regions, with patterns of damage varying among ALS subtypes. These findings support the use of neuroimaging in ALS diagnosis and monitoring. Biomarkers such as neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNFH) have shown promise in diagnosing and monitoring ALS. Recent studies have also explored the role of inflammatory biomarkers and metabolic indicators in ALS progression. Overall, the field of ALS research is rapidly evolving, with new genetic discoveries, advanced imagingRecent advances in understanding the molecular mechanisms of amyotrophic lateral sclerosis (ALS) have enabled the translation of novel research findings into clinical practice, including gene therapy approaches. The field has also seen significant improvements in assistive technologies, allowing for more personalized supportive and symptomatic care. This review summarizes recent studies on ALS pathogenesis, clinical trial results, and future directions for improving clinical management. ALS, a severe motor neuron disease, involves both upper and lower motor neurons and is influenced by genetic and environmental factors. Recent studies confirm that ALS incidence is highest in Europe, with increasing trends in Ireland, Scotland, and parts of Italy. In Asia, while overall incidence is lower than in Europe and North America, the prevalence is second only to that of Western Europe, possibly due to genetic differences. The sex ratio in ALS is slightly higher in males, though recent studies suggest a more balanced ratio. The role of sex hormones, environmental exposure, and sex chromosomes may contribute to this difference. Over 40 genes have been associated with ALS, with SOD1, C9orf72, TARDBP, and FUS being the most common. The C9orf72 hexanucleotide repeat expansion is the most common genetic cause in European familial ALS, accounting for over 30% of cases. Recent studies have identified additional genes, such as TBK1, NEK1, and DNAJC7, as potential ALS-related genes. Haploinsufficiency is a shared mechanism among several ALS-related genes, and recent studies have identified new genetic risk factors, such as SUMO4 haploinsufficiency. Environmental factors, including smoking, alcohol consumption, and occupational exposures, have been associated with ALS risk. However, age, male gender, and family history remain the most well-established risk factors. Physical activity and head trauma may also play a role, though the relationship is complex and requires further study. ALS exhibits significant clinical and phenotypic heterogeneity, with various subtypes such as bulbar, flail arm, and respiratory onset ALS. Cognitive and behavioral changes are common in up to half of ALS patients, with some cases meeting criteria for frontotemporal dementia (FTD). These changes can significantly impact patient survival, quality of life, and caregiver burden. Neuroimaging techniques have advanced, providing insights into ALS pathogenesis and progression. Structural and functional imaging have shown early involvement of the corticospinal tract and other brain regions, with patterns of damage varying among ALS subtypes. These findings support the use of neuroimaging in ALS diagnosis and monitoring. Biomarkers such as neurofilament light chain (NfL) and phosphorylated neurofilament heavy chain (pNFH) have shown promise in diagnosing and monitoring ALS. Recent studies have also explored the role of inflammatory biomarkers and metabolic indicators in ALS progression. Overall, the field of ALS research is rapidly evolving, with new genetic discoveries, advanced imaging