肌萎缩侧索硬化症（ALS）是一种无法治愈的神经退行性疾病，会影响上、下运动神经元，导致肌肉无力、运动障碍、残疾和死亡。大约5-10%的ALS病例与积极的家族病史有关（家族性ALS或fALS），而其余的是散发性（散发性ALS或sALS）。已确定50个基因可作为ALS的病因或风险因素。已知的致病变体包括超氧化物歧化酶1型（SOD1）、染色体9开放阅读框72（c9orf72）、TAR DNA结合蛋白（TARDBP）和融合在肉股上的蛋白（FUS）；还发现了额外的与ALS相关基因，包括带电多囊体蛋白2B（CHMP2B）、天蛇酸酵素（SETX）、分泌体1（SQSTM1）、恶性肿瘤相关激酶1（TBK1）和NIMA相关激酶1（NEK1）。这些基因的突变可能影响不同的机制，包括囊泡运输、自噬以及细胞骨架或线粒体功能。到目前为止，还没有针对ALS的有效疗法。因此，早期诊断和疾病风险预测仍然是对抗ALS症状的最佳选择之一。蛋白质组学生物标志物、微小RNA和细胞外囊泡作为诊断或疾病进展评估的有希望的工具。这些标志物相对容易从血液或脑脊液中获取，并可用于在临床症状出现之前的临床前阶段识别潜在的遗传病因和风险因素。此外，反义寡核苷酸和RNA基因疗法已成功用于治疗其他疾病，如儿童早发性脊髓性肌萎缩症（SMA），这也为ALS患者带来了希望。因此，应生成一个有效的基因和生物标志物组，以为可能“有风险”的个体提供及时干预，并尽快改善ALS患者的治疗结果。

Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease affecting the upper and lower motor neurons, leading to muscle weakness, motor impairments, disabilities and death. Approximately 5-10% of ALS cases are associated with positive family history (familial ALS or fALS), whilst the remainder are sporadic (sporadic ALS, sALS). At least 50 genes have been identified as causative or risk factors for ALS. Established pathogenic variants include superoxide dismutase type 1 (SOD1), chromosome 9 open reading frame 72 (c9orf72), TAR DNA Binding Protein (TARDBP), and Fused In Sarcoma (FUS); additional ALS-related genes including Charged Multivesicular Body Protein 2B (CHMP2B), Senataxin (SETX), Sequestosome 1 (SQSTM1), TANK Binding Kinase 1 (TBK1) and NIMA Related Kinase 1 (NEK1), have been identified. Mutations in these genes could impair different mechanisms, including vesicle transport, autophagy, and cytoskeletal or mitochondrial functions. So far, there is no effective therapy against ALS. Thus, early diagnosis and disease risk predictions remain one of the best options against ALS symptomologies. Proteomic biomarkers, microRNAs, and extracellular vehicles (EVs) serve as promising tools for disease diagnosis or progression assessment. These markers are relatively easy to obtain from blood or cerebrospinal fluids and can be used to identify potential genetic causative and risk factors even in the preclinical stage before symptoms appear. In addition, antisense oligonucleotides and RNA gene therapies have successfully been employed against other diseases, such as childhood-onset spinal muscular atrophy (SMA), which could also give hope to ALS patients. Therefore, an effective gene and biomarker panel should be generated for potentially "at risk" individuals to provide timely interventions and better treatment outcomes for ALS patients as soon as possible.