Recent works have demonstrated an expansion of the GGGGCC hexanucleotide repeat 
in the first intron of chromosome 9 open reading frame 72 (C9ORF72), encoding an 
unknown C9ORF72 protein, which was responsible for an unprecedented large 
proportion of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia 
(FTD) cases of European ancestry. C9ORF72 is expressed in most tissues including 
the brain. Emerging evidence has demonstrated that C9ORF72 mutations could 
reduce the level of C9ORF72 variant 1, which may influence protein expression 
and the formation of nuclear RNA foci. The spectrum of mutations is broad and 
provides new insight into neurological diseases. Clinical manifestations of 
diseases related with C9ORF72 mutations can vary from FTD, ALS, primary lateral 
sclerosis (PLS), progressive muscular atrophy (PMA), Huntington disease-like 
syndrome (HDL syndrome), to Alzheimer's disease. In this article, we will review 
the brief characterizations of the C9ORF72 gene, the expansion mutations, the 
related disorders, and their features, followed by a discussion of the 
deficiency knowledge of C9ORF72 mutations. Based on the possible pathological 
mechanisms of C9ORF72 mutations in ALS and FTD, we can find new targets for the 
treatment of C9ORF72 mutation-related diseases. Future studies into the 
mechanisms, taking into consideration the discovery of those disorders, will 
significantly accelerate new discoveries in this field, including targeting 
identification of new therapy.