C9orf72 and amyotrophic lateral sclerosis: Antisense oligonucleotides (ASOs) such as IONIS-C9Rx and CRISPR-Cas9-mediated repeat deletion have shown efficacy in animal models, yet clinical translation faces challenges: (1) C9orf72 is widely expressed in microglia and astrocytes, raising concerns about systemic gene editing disrupting immune function; (2) 90% of ALS cases are sporadic, with mechanisms diverging from C9orf72-linked pathology, necessitating broad-spectrum therapies.